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Lymphland International Lymphedema Online
February 1, 2011
Int J Gynecol Cancer. 2011 Feb;21(2):409-18.
Assessment of bilateral limb lymphedema by bioelectrical impedance spectroscopy.
Ward L, Winall A, Isenring E, Hills A, Czerniec S, Dylke E, Kilbreath S.
Abstract
OBJECTIVE: : The aim of the present study was to determine if the ratio of extracellular fluid (ECF),
including the lymph, to that of intracellular fluid (ICF), as measured by bioimpedance spectroscopy (BIS),
could be used to assess bilateral lymphedema (LE).
BACKGROUND: : The presence of LE is commonly determined as an increase in tissue volume due to the
presence of excess lymph relative to the volume of a comparable unaffected body region or to comparative
normative data. However, in bilateral LE of the limbs, a comparable body region, the contralateral limb, is
also affected, precluding normalization. An alternative is to normalize the increase in lymph volume, as ECF,
to that of ICF volume.
METHODS: : Extracellular/intracellular fluid ratios, expressed as the ratio of intracellular impedance (Ri) to
extracellular impedance (R0), for the limbs of 277 female and 224 male controls were determined from an
accumulated database of impedance data. Equivalent data were obtained for an opportunistic cross-
sectional sample of 37 female and 5 male participants with bilateral LE of the legs. The ratios of Ri/R0 in the
lymphedematous legs of the affected participants were compared with the equivalent ratios in the unaffected
arms of the same participants and with those of the controls using box plots and visualized as bivariate data
using tolerance ellipses.
RESULTS: : Despite Ri/R0 ratios varying with age, sex, and limb dominance, comparison of the ratio for
affected legs (normalized to the ratio in the unaffected arms) with equivalent ratios observed in a control
population (as bivariate tolerance plots) was capable of discriminating between 70% and 89% of the
participants with LE.
CONCLUSIONS: : Bioelectrical impedance spectroscopy and determination of Ri/R0 ratios as indices of
ECF/ICF ratios holds promise for the semiquantitative assessment of bilateral LE.
PMID: 21270623 [PubMed - in process]
Int J Gynecol Cancer. 2011 Feb;21(2):385-90.
A Retrospective Analysis of Postoperative Complications With or Without Para-aortic Lymphadenectomy
in Endometrial Cancer.
Konno Y, Todo Y, Minobe S, Kato H, Okamoto K, Sudo S, Takeda M, Watari H, Kaneuchi M, Sakuragi
N.
*Department of Obstetrics and Gynaecology, Hokkaido University School of Medicine, Sapporo, Japan;
and †Division of Gynecologic Oncology, National Hospital Organization, Hokkaido Cancer Center,
Sapporo, Japan.
Abstract
INTRODUCTION: : Although para-aortic lymphadenectomy (PALX) has not been accepted as a standard
treatment for patients with endometrial cancer, it is possible that systematic lymphadenectomy including
PALX has therapeutic significance for patients with intermediate-/high-risk endometrial cancer. On the other
hand, a consensus regarding the safety of PALX has not been reached. The aim of this study was to
compare the incidence rates of postoperative complications after pelvic lymphadenectomy (PLX) with or
without PALX in patients with uterine corpus cancer.
METHODS: : A retrospective chart review was carried out for all patients with endometrial cancer treated
at 2 tertiary centers between 1998 and 2004. Surgery at one institute included both PLX and PALX,
whereas PLX alone was routinely performed at the other institute. A total of 142 patients underwent PLX +
PALX and 138 patients underwent PLX alone. We evaluated postoperative complications including
intraoperative injury, ileus, lymphedema, lymphocyst, and thrombosis.
RESULTS: : There was no fatal accident associated with surgery. Lymphedema was the most frequent
complication. Comparing the PLX + PALX group and the PLX group, there were no significant differences
in the rate of cases of lymphedema (23.2% vs 28.3%), lymphocyst (9.2% vs 9.4%), and thrombosis (4.9%
vs 2.2%). The rate of cases of mild/moderate ileus in the PLX + PALX group was significantly higher than
that in the PLX group (10.5% vs 2.9%; P = 0.011). However, no significant difference in the rates of cases
of severe ileus was found between the 2 groups (1.4% vs 0.7%). There were also no significant differences
between the 2 groups in the rates of intraoperative organ injury (2.8% vs 2.2%) and secondary operation
for postoperative complications (4.9% vs 4.3%).
CONCLUSIONS: : Para-aortic lymphadenectomy can be performed with an acceptable morbidity under
the conditions in which it is performed by experienced surgeons, and measures to prevent complications are
properly taken.
PMID: 21270621 [PubMed - in process]
Eur J Surg Oncol. 2011 Mar;37(3):187-98. Epub 2011 Jan 26.
Positron emission tomography (PET) for assessment of axillary lymph node status in early breast cancer: A
systematic review and meta-analysis.
Cooper KL, Harnan S, Meng Y, Ward SE, Fitzgerald P, Papaioannou D, Wyld L, Ingram C, Wilkinson
ID, Lorenz E.
School of Health and Related Research (ScHARR), University of Sheffield, Regent Court, 30 Regent
Street, Sheffield S1 4DA, UK.
Abstract
PURPOSE: Sentinel lymph node biopsy (SLNB) and axillary lymph node dissection (ALND) are used to
assess axillary nodal status in breast cancer, but are invasive procedures associated with morbidity, including
lymphoedema. This systematic review evaluates the diagnostic accuracy of positron emission tomography
(PET), with or without computed tomography (CT), for assessment of axillary nodes in early breast cancer.
METHODS: Eleven databases including MEDLINE, EMBASE and the Cochrane Library, plus research
registers and conference proceedings, were searched in April 2009. Study quality was assessed using the
QUality Assessment of Diagnostic Accuracy Studies (QUADAS) checklist. Sensitivity and specificity were
meta-analysed using a bivariate random effects approach.
RESULTS: Across 26 studies evaluating PET or PET/CT (n = 2591 patients), mean sensitivity was 63%
(95% CI: 52-74%; range 20-100%) and mean specificity 94% (95% CI: 91-96%; range 75-100%).
Across 7 studies of PET/CT (n = 862), mean sensitivity was 56% (95% CI: 44-67%) and mean specificity
96% (90-99%). Across 19 studies of PET-only (n = 1729), mean sensitivity was 66% (50-79%) and mean
specificity 93% (89-96%). Mean sensitivity was 11% (5-22%) for micrometastases (=2 mm; five studies; n
= 63), and 57% (47-66%) for macrometastases (>2 mm; four studies; n = 111).
CONCLUSIONS: PET had lower sensitivity and specificity than SLNB. Therefore, replacing SLNB with
PET would avoid the adverse effects of SLNB, but lead to more false negative patients at risk of recurrence
and more false positive patients undergoing unnecessary ALND. The present evidence does not support the
routine use of PET or PET-CT for the assessment of the clinically negative axilla.
Crown Copyright © 2011. Published by Elsevier Ltd. All rights reserved.
PMID: 21269795 [PubMed - in process]
February 4, 2011
Circulation. 2011 Jan 31. [Epub ahead of print]
Growth Factor Therapy and Autologous Lymph Node Transfer in Lymphedema.
Lähteenvuo M, Honkonen K, Tervala T, Tammela T, Suominen E, Lähteenvuo J, Kholová I, Alitalo K, Ylä-
Herttuala S, Saaristo A.
Department of Biotechnology and Molecular Medicine, A.I. Virtanen Institute for Molecular Sciences,
University of Eastern Finland, Kuopio.
Abstract
Background- Lymphedema after surgery, infection, or radiation therapy is a common and often incurable
problem. Application of lymphangiogenic growth factors has been shown to induce lymphangiogenesis and
to reduce tissue edema. The therapeutic effect of autologous lymph node transfer combined with adenoviral
growth factor expression was evaluated in a newly established porcine model of limb lymphedema. Methods
and Results- The lymphatic vasculature was destroyed within a 3-cm radius around an inguinal lymph node.
Lymph node grafts and adenovirally (Ad) delivered vascular endothelial growth factor (VEGF)-C (n=5) or
VEGF-D (n=9) were used to reconstruct the lymphatic network in the inguinal area; AdLacZ (ß-
galactosidase; n=5) served as a control. Both growth factors induced robust growth of new lymphatic
vessels in the defect area, and postoperative lymphatic drainage was significantly improved in the VEGF-
C/D-treated pigs compared with controls. The structure of the transferred lymph nodes was best preserved
in the VEGF-C-treated pigs. Interestingly, VEGF-D transiently increased accumulation of seroma fluid in the
operated inguinal region postoperatively, whereas VEGF-C did not have this side effect. Conclusions-
These results show that growth factor gene therapy coupled with lymph node transfer can be used to repair
damaged lymphatic networks in a large animal model and provide a basis for future clinical trials of the
treatment of lymphedema.
PMID: 21282502 [PubMed - as supplied by publisher]
Clin J Oncol Nurs. 2011 Feb 1;15(1):99-101.
Cutaneous metastases in breast cancer.
Kalmykow B, Walker S.
Prostate Cancer Care Center, Beth Israel Deaconess Medical Center, Boston, MA.
Abstract
Cutaneous metastases occur more often in breast cancer than in other diseases in women. Presentation often
is ambiguous because the metastases can mimic other common processes (e.g., cellulitis, lymphedema).
Accurate differential diagnosis identifies less obvious manifestations of progressive disease and allows for
appropriate management. Although interventions are aimed at halting disease progression, cutaneous
metastases indicate an incurable diagnosis. Treatment focuses on delaying progressive disease, controlling
symptoms, and maintaining quality of life. The care of skin metastases evolves as the tumor spreads and
more tissue destruction occurs. Skin management and topical interventions increase comfort, decrease
distress, and create feelings of control in this population.
PMID: 21278046 [PubMed - in process]
Int J Surg. 2011 Jan 27. [Epub ahead of print]
Mathematical model to predict risk for lymphoedema after treatment of cutaneous melanoma.
Campanholi LL, Duprat Neto JP, Fregnani JH.
AC Camargo Hospital, São Paulo, Brazil.
Abstract
AIM: To evaluate risk factors for lymphoedema development in the upper and lower limbs and to propose a
model that predicts risk of lymphoedema after lymphadenectomy.
PATIENTS: We studied 84 patients who had undergone radical lymphadenectomies for cutaneous
melanoma from 1990 to 2008.
METHODS: The patients included underwent an evaluation that consisted of measurement of limb volume
using perimetry, application of the manually acquired perimetric data to the truncated-cone formula, and data
from medical records.
RESULTS: Using multivariate analysis, we obtained the following risk factors for the development of
lymphoedema: reconstruction with graft (p=0.013), Breslow depth >4mm (p=0.029), ilioinguinal
lymphadenectomy (p=0.037) and wound infection (p=0.036). We assigned points to each factor as dictated
by the value of the regression coefficient, as follows: infection (1 point), ilioinguinal lymphadenectomy and
Breslow >4mm (2 points each) and reconstruction with graft (3 points). The mathematical model for
predicting lymphoedema risk in the limb ipsilateral to the lymphadenectomy was based on risk groups,
defined by score: low risk=0 point (for which we calculated an 8.3% chance of developing lymphoedema),
intermediate risk=1-2 points (26.8%), high risk=3 points (52.9%) and very high risk=4 or more points
(88.9%).
CONCLUSIONS: This study identified a melanoma thickness >4mm, graft reconstruction, ilioinguinal
lymphadenectomy and infection as risk factors for lymphoedema. From these factors, we constructed a
mathematical model that successfully predicted risk of post-lymphadenectomy lymphoedema. The combined
presence of these risk factors increased the chance of developing lymphoedema.
Copyright © 2011 Surgical Associates Ltd. Published by Elsevier Ltd. All rights reserved.
PMID: 21276878 [PubMed - as supplied by publisher]
Health Technol Assess. 2011 Jan;15(4):1-134.
Positron emission tomography (PET) and magnetic resonance imaging (MRI) for the assessment of axillary
lymph node metastases in early breast cancer: systematic review and economic evaluation.
Cooper K, Meng Y, Harnan S, Ward S, Fitzgerald P, Papaioannou D, Wyld L, Ingram C, Wilkinson I,
Lorenz E.
School of Health and Related Research (ScHARR), University of Sheffield, Sheffield, UK.
Abstract
BACKGROUND: Breast cancer is the most common type of cancer in women. Evaluation of axillary lymph
node metastases is important for breast cancer staging and treatment planning.
OBJECTIVES: To evaluate the diagnostic accuracy, cost-effectiveness and effect on patient outcomes of
positron emission tomography (PET), with or without computed tomography (CT), and magnetic resonance
imaging (MRI) in the evaluation of axillary lymph node metastases in patients with newly diagnosed early-
stage breast cancer.
DATA SOURCES: A systematic review of literature and an economic evaluation were carried out. Key
databases (including MEDLINE, EMBASE and nine others) plus research registers and conference
proceedings were searched for relevant studies up to April 2009. A decision-analytical model was
developed to determine cost-effectiveness in the UK.
REVIEW METHODS: One reviewer assessed titles and abstracts of studies identified by the search
strategy, obtained the full text of relevant papers and screened them against inclusion criteria. Data from
included studies were extracted by one reviewer using a standardised data extraction form and checked by
a second reviewer. Discrepancies were resolved by discussion. Quality of included studies was assessed
using the quality assessment of diagnostic accuracy studies (QUADAS) checklist, applied by one reviewer
and checked by a second.
RESULTS: Forty-five citations relating to 35 studies were included in the clinical effectiveness review: 26
studies of PET and nine studies of MRI. Two studies were included in the cost-effectiveness review: one of
PET and one of MRI. Of the seven studies evaluating PET/CT (n = 862), the mean sensitivity was 56%
[95% confidence interval (CI) 44% to 67%] and mean specificity 96% (95% CI 90% to 99%). Of the 19
studies evaluating PET only (n = 1729), the mean sensitivity was 66% (95% CI 50% to 79%) and mean
specificity 93% (95% CI 89% to 96%). PET performed less well for small metastases; the mean sensitivity
was 11% (95% CI 5% to 22%) for micrometastases (= 2 mm; five studies; n = 63), and 57% (95% CI
47% to 66%) for macrometastases (> 2 mm; four studies; n = 111). The smallest metastatic nodes detected
by PET measured 3 mm, while PET failed to detect some nodes measuring > 15 mm. Studies in which all
patients were clinically node negative showed a trend towards lower sensitivity of PET compared with
studies with a mixed population. Across five studies evaluating ultrasmall super-paramagnetic iron oxide
(USPIO)-enhanced MRI (n = 93), the mean sensitivity was 98% (95% CI 61% to 100%) and mean
specificity 96% (95% CI 72% to 100%). Across three studies of gadolinium-enhanced MRI (n = 187), the
mean sensitivity was 88% (95% CI 78% to 94%) and mean specificity 73% (95% CI 63% to 81%). In the
single study of in vivo proton magnetic resonance spectroscopy (n = 27), the sensitivity was 65% (95% CI
38% to 86%) and specificity 100% (95% CI 69% to 100%). USPIO-enhanced MRI showed a trend
towards higher sensitivity and specificity than gadolinium-enhanced MRI. Results of the decision modelling
suggest that the MRI replacement strategy is the most cost-effective strategy and dominates the baseline 4-
node sampling (4-NS) and sentinel lymph node biopsy (SLNB) strategies in most sensitivity analyses
undertaken. The PET replacement strategy is not as robust as the MRI replacement strategy, as its cost-
effectiveness is significantly affected by the utility decrement for lymphoedema and the probability of relapse
for false-negative (FN) patients.
LIMITATIONS: No included studies directly compared PET and MRI.
CONCLUSIONS: Studies demonstrated that PET and MRI have lower sensitivity and specificity than
SLNB and 4-NS but are associated with fewer adverse events. Included studies indicated a significantly
higher mean sensitivity for MRI than for PET, with USPIO-enhanced MRI providing the highest sensitivity.
However, sensitivity and specificity of PET and MRI varied widely between studies, and MRI studies were
relatively small and varied in their methods; therefore, results should be interpreted with caution. Decision
modelling based on these results suggests that the most cost-effective strategy may be MRI rather than
SLNB or 4-NS. This strategy reduces costs and increases quality-adjusted life-years (QALYs) because
there are fewer adverse events for the majority of patients. However, this strategy leads to more FN cases
at higher risk of cancer recurrence and more false- positive (FP) cases who would undergo unnecessary
axillary lymph node dissection. Adding MRI prior to SLNB or 4-NS has little effect on QALYs, though this
analysis is limited by lack of available data. Future research should include large, well-conducted studies of
MRI, particularly using USPIO; data on the long-term impacts of lymphoedema on cost and patient utility;
studies of the comparative effectiveness and cost-effectiveness of SLNB and 4-NS; and more robust UK
cost data for 4-NS and SLNB as well as the cost of MRI and PET techniques.
FUNDING: This study was funded by the Health Technology Assessment programme of the National
Institute of Health Research.
PMID: 21276372 [PubMed - in process]
Int Angiol. 2010 Oct;29(5):391-470.
Compression therapy. Proceedings of a meeting organized by the International Compression Club.
September 2008.
Lucca, Italy.
[No authors listed]
PMID: 21275106 [PubMed - indexed for MEDLINE]
February 9, 2011
J Cutan Med Surg. 2011 Jan-Feb;15(1):61-2.
An approach to the treatment of vulvar lymphedema.
Bourgeault E, Giroux L.
PMID: 21291658 [PubMed - in process]
Dermatological and soft-tissue manifestations of Fabry disease: characteristics and response to enzyme
replacement therapy.
Lidove O, Jaussaud R, Aractingi S.
In: Mehta A, Beck M, Sunder-Plassmann G, editors. Fabry Disease: Perspectives from 5 Years of FOS.
Oxford: Oxford PharmaGenesis; 2006. Chapter 24.
Excerpt
Early manifestations of Fabry disease include dermatological and soft-tissue symptoms, such as
angiokeratomas, acroparaesthesia, abnormal sweating (hypohidrosis and hyperhidrosis) and lymphoedema.
Recognition of these symptoms is vital for the early diagnosis and treatment of Fabry disease. It is therefore
important that dermatologists, as well as other specialists, are aware of the manifestations of Fabry disease.
Clinical studies and data from FOS – the Fabry Outcome Survey – have suggested that enzyme replacement
therapy with agalsidase alfa can improve sweating, heat intolerance and pain in patients with Fabry disease.
Copyright © 2006, Oxford PharmaGenesis™
Sections
Introduction
Pathology of cutaneous lesions in Fabry disease
Sweating
Lymphoedema
Acroparaesthesia
Facial dysmorphia
Response to ERT
Conclusions
References
PMID: 21290701 [PubMed]
February 11, 2011
ANZ J Surg. 2011 Jan;81(1-2):103-4. doi: 10.1111/j.1445-2197.2010.05625.x.
Massive localized lymphoedema.
Jones M, Marshall D, Mason D.
Anaesthetics Department, South Devon Healthcare NHS Foundation Trust, Torquay, Devon, UK.
PMID: 21299819 [PubMed - in process]
MED NEWS DOCUMENT FORMATTED:
February 10, 2011
Photodynamic Ablation Of Lymphatic Vessels And Intralymphatic Cancer Cells Prevents Metastasis
Tumor cells have several routes that enable them to move from the primary tumor to distant tissues, a
process called metastasis. It is metastasis of the primary tumor that kills most cancer patients. One of the
least studied routes of metastasis is the lymphatic system. Many tumors produce factors that promote the
formation of new lymphatic vessels (lymphangiogenesis). The newly formed lymphatic vessels enable tumor
cells to travel from the primary tumor to the regional lymph nodes from whence they can spread throughout
the body.
Current treatment practice is to surgically remove the primary tumor as well as the metastatic lymph nodes,
but tumor cells in metastatic transit inside the lymphatic vessels had not been given much attention.
In a new study, Dr Tuomas Tammela and colleagues at the University of Helsinki, Finland, investigated
whether eradicating tumor-associated lymphatic vessels and the tumor cells they contain using photodynamic
therapy (PDT) with a light-activated cytotoxic drug could reduce or eliminate tumor metastasis. They
selected the mouse ear as their model system because it is easy to image both the lymphatic vessels and the
in-transit tumor cells.
The researchers implanted mouse melanoma cells or human lung tumor cells into the mouse ear tip and
waited two weeks for the primary tumors to become established and to induce lymphangiogenesis. Using
deep-tissue microscopy, they observed that the newly formed lymphatic vessels contained in-transit tumor
cells as well as small tumor nodules. Using pathology sections taken from a patient with recurrent melanoma,
they confirmed that the tumor-associated lymphatic vessels of cancer patients contain in-transit tumor cells
and tumor nodules.
However, could PDT eliminate both tumor-associated lymphatic vessels and the tumor cells inside them?
The researchers injected verteporfin in a liposomal preparation intradermally into the mouse ear and showed
that this cytotoxic dye accumulated specifically in the lymphatic vessels. When they illuminated the mouse ear
with infrared laser light, the lymphatic vessels started to shrink and fragment, and became leaky. Also, the
researchers found that the mice receiving PDT and surgery had a much lower relapse rate than those that
underwent surgery alone.
Using a pig model, the researchers also showed that PDT can target lymphatic vessels deep within the body
and, thus, PDT could be useful eradicating tumor-associated lymphatic vessels deep within the tissues of
human cancer patients.
"These findings are new and exciting, because the cells in metastatic transit in tumor-draining lymphatic
vessels have not been given much attention previously", Dr. Tammela says.
"We do not expect PDT to replace current surgical techniques, which comprise removal of the primary
tumor and metastatic lymph nodes. However, PDT could easily be combined with existing surgical
techniques to destroy the lymphatic vessels draining from the tumor, as well as the tumor cell aggregates
residing within them."
PDT using verteporfin is currently used clinically to destroy overgrown blood vessels in the retina of patients
with macular degeneration. As both the drug and the PDT concept are already in use in patients, they are
more likely to receive regulatory approval for targeting tumor-associated lymphatic vessels in cancer patients
undergoing surgery than drugs still in earlier phases of development, Tammela states.
Source:
Dr. Tuomas Tammela
University of Helsinki
February 23, 2011 - Myofascial Release effective for many physical conditions - Coeur d'Alene Press – By
VIRGINIA TAFT –
Myofascial Release is used to treat acute pain due to accident or injury as well as chronic neck, back, sciatic
pain. It is also used to treat arthritis, Fibromyalgia, sciatica, TMJ, post surgical scar and lymphedema, just to
name a few. Myofascial Release or "MFR" is a very effective hands-on technique that provides sustained
pressure into myofascial restrictions to eliminate pain and restore motion.
It also allows the body to move to release holding patterns.
To understand this technique it is important to understand the fascial system. Myo, means muscle, and fascia
(pronounced "fasha") is the connective tissue. The fascia is a specialized system of the body that has an
appearance similar to a spider's web or a sweater. Fascia is very densely woven, covering and
interpenetrating every muscle, bone, nerve, artery and vein as well as all of our internal organs including
heart, lungs, brain ad spinal cord.
The most interesting aspect of the fascial system is that it is not just a system of separate coverings. It is
actually one structure that exists from head to foot without interruption. In this way, you can begin to see that
each part of the entire body is connected to every other part by the fascia, like the yarn in a sweater.
Fascia also plays an important role in the support of our bodies, since it surrounds and attaches to all
structures. These structures would not be able to provide stability without the constant pull of the fascial
system. In fact, our bones can be thought of as tent poles, which cannot support the structure without the
constant support of the guide wires (or fascia) to keep an adequate amount of tension to allow the tent (or
body) to remain upright with proper equilibrium.
Trauma, such as a fall, whiplash or surgery can cause tight areas in the fascia. This system is also affected by
repetitive motions or just habitual poor posture over time, which have a cumulative effect. The changes
caused in the fascial system influence the skeletal framework for our posture. The fascia can exert excessive
pressure producing pain or restriction of motion, decreased flexibility and is a determining factor in our ability
to withstand stress and strain.
Myofascial Release is a gentle, safe and highly effective, whole body, "hands on" approach. It allows us to
look at each patient as unique with focus on the whole body rather than just the injured part.
Often where we feel pain, is not where the problem really is located. MFR utilizes varying pressure from
heavy to light to eliminate pain and restore motion as well as deepens the relaxation response.
Patients may be seen one-on-one with a therapist or may opt for co-treatments with two therapists.
During these hands-on treatments therapists use may use other manual techniques and movement therapy.
The patient is an active participant in the treatment program. Each patient is given a home program to
maximize benefit from therapy. This promotes independence though education in proper body mechanics,
enhancement of strength, flexibility, as well as postural and movement awareness.
Coeur d' Alene Hand Therapy and Healing Center specializes in Advanced Myofascial Release and manual
therapy techniques. Call (208) 664-2901 for more information or to receive a free consultation
February 19, 2011
Am J Dermatopathol. 2011 Feb 1. [Epub ahead of print]
Lymphangiectases Are Common Underlying Warts and in Normal Peritumoral Skin: Histologic Evidence of
Decreased Immune Surveillance.
Paul J, Carlson JA.
From the Divisions of Dermatopathology and Dermatology, Department of Pathology, Albany Medical
Center, Albany, NY.
Abstract
BACKGROUND: Lymphangiectases are a histologic sign of lymphostasis, which is associated with
decreased immune cell trafficking and cell-mediated immunity.
OBJECTIVE: To determine if latent lymphedema is apparent underlying warts and in skin affected by
cutaneous neoplasia.
MATERIALS AND METHODS: The number and maximal dilation of lymphangiectases were measured in
the upper half of the dermis of 51 consecutive biopsies of warts, 230 consecutive normal skin samples from
primary skin tumor excisions, and 14 normal skin samples from breast reduction (11) and panniculectomy
(3) specimens.
RESULTS: All warts had one or more underlying lymphangiectases compared with 79% of peritumor
normal skin samples and 50% of cosmetic specimens. The mean number of lymphangiectases and mean
maximal dilation were significantly greater in warts than in peritumor skin, which was significantly greater than
cosmetic skin samples (3.6 vs. 1.3 vs. 0.12 lymphangiectases per square millimeter and 54 vs. 23 vs. 1 µm,
respectively; P = 0.0001). Warts exhibited mild fibrosis significantly more frequently than peritumor skin
(57% vs. 5%; P = 0.0001). For peritumor (normal) skin, age, solar elastosis, and adjacent malignancy
correlated with greater dilation of lymphatics. Solar elastosis also correlated with increased number of
lymphangiectases.
CONCLUSIONS: Minor trauma and solar elastosis from chronic ultraviolet radiation exposure are likely
the etiologic factors in the development of lymphostasis. By decreasing immune surveillance, latent
lymphedema ostensibly facilitates human papillomavirus infection and carcinogenesis.
PMID: 21317613 [PubMed - as supplied by publisher]
Cesk Patol. 2010 Oct;46(4):98-103.
[Lymphatic system: morphology and pathology update].
[Article in Czech]
Kholová I.
Pathology, Laboratory Centre, Tampere University Hospital, Tampere, Finland. ivana.kholova@sll.fimnet.fi
Abstract
The lymphatic system is crucial for the maintenance of tissue fluid balance, immune surveillance, and fatty
acids absorption in the intestine. The lymphatic vessels are also involved in the pathogenesis of tumor
metastasis, lymphedema, and various inflammatory processes. Recently, several markers specific for
lymphatic endothelium were found. Progress in the field of lymphatic growth factors and their receptors, and
molecular lymphatic biology has helped to understand better the lymphatic vasculature. This review
summarizes the updates on lymphatic system research and possible applications in routine pathological
diagnostics.
PMID: 21313736 [PubMed - in process]
February 22, 2011
Adv Ther. 2011 Feb 14. [Epub ahead of print]
Merino wool graduated compression stocking increases lower limb venous blood flow: A randomized
controlled trial.
Charles T, Mackintosh D, Healy B, Perrin K, Weatherall M, Beasley R.
Medical Research Institute of New Zealand, Private Bag 7902, Wellington, 6242, New Zealand, Thom.
Charles@mrinz.ac.nz.
Abstract
INTRODUCTION: Graduated compression stockings represent a nonpharmacological approach to reduce
the risk of deep vein thrombosis (DVT) and pulmonary embolism (PE) due to prolonged immobility through
reducing lower limb venous stasis. A novel merino wool, double-layer, below-knee graduated compression
stocking has been developed to reduce the risk of air travel-related DVT and PE.
METHODS: Twenty healthy adult participants were randomized to wear the novel graduated compression
stocking on either the left or right leg. Doppler ultrasound measurements of popliteal venous blood flow
were made on both legs over a 120-minute period. The primary outcome was peak systolic velocity in the
popliteal vein at 120 minutes. Secondary outcomes included mean flow velocity, total volume flow, vein
cross-sectional area, and change in ankle and calf measurements.
RESULTS: The popliteal vein peak systolic velocity was 0.35 cm/s (95% confidence intervals [CI], 0.22 to
0.49, P<0.001) higher with stocking use at 120 minutes, a difference of 24%. Mean flow velocity and total
volume flow were also significantly higher with stocking use. Ankle and calf circumference were decreased
with stocking use, with an overall difference of -6.3 mm (95% CI, -11.3 to -1.2, P=0.021) and -7.9 mm
(95% CI, -13.3 to -2.4, P=0.011), respectively.
CONCLUSION: The novel merino wool double-layer, below-knee graduated compression stocking
increases lower limb venous blood flow during prolonged seated immobility. Its use is likely to reduce the
risk of DVT and PE in situations of prolonged seated immobility, such as long-distance air travel. The
reduction in lower limb swelling associated with their use suggests that the stockings are likely to have utility
in the treatment of chronic venous insufficiency and lymphedema.
PMID: 21331557 [PubMed - as supplied by publisher]
Breast Cancer. 2011 Feb 18. [Epub ahead of print]
Lymphedema and breast cancer: a review of the literature.
Michael S, Charikleia S, Konstantinos K.
4th Department of Surgery, Medical School, Attikon General Hospital, University of Athens, Athens,
Greece, mixalislak@gmail.com.
Abstract
Breast cancer continues to be the most common malignancy among women in the United States. Despite its
high incidence, early detection and modern treatment have made long-term survival more common. One of
the most important sequelae of the treatment of breast cancer is the development of lymphedema. There are
many issues for women to deal with after treatment for breast cancer. Focusing on the quality of life after
breast cancer means dealing with issues such as an altered body image, changes in relationships with partner
and children, living with any ongoing side effects, and the fear of tumor recurrence. The objective of this
paper is to elucidate these issues concerning lymphedema.
PMID: 21331463 [PubMed - as supplied by publisher]
Scand J Urol Nephrol. 2011 Feb 18. [Epub ahead of print]
Management of diuretic treatment: A challenge in the obese patient.
Lassen CK, Jespersen B.
Department of Nephrology, Aarhus University Hospital, Skejby, Brendstrupgårdsvej 100, DK-8200
Aarhus N, Skejby, Denmark.
Abstract
Abstract The obesity epidemic is a major health concern. The diagnosis of acute illness and fluid imbalance
in the obese patient is complicated by a wide range of comorbidities such as cardiovascular disease, obesity
hypoventilation syndrome, non-alcoholic steatohepatitis and lymphoedema. Thus, obesity warrants
particularly careful clinical and biochemical assessment owing to its resemblance to fluid retention. Dosing of
diuretics is difficult in these patients. The blood urea:creatinine ratio should be widely used to detect
emerging cardiovascular and renal complications. This report presents an obese patient with congestive heart
failure due to a myocardial infarction, who subsequently was overdosed with diuretics. His prerenal acute
renal failure resolved when diuretics were stopped and the high urea:creatinine ratio was diagnostic.
PMID: 21329483 [PubMed - as supplied by publisher]
Cochrane Database Syst Rev. 2011 Feb 16;2:CD001899.
Intermittent pneumatic compression for treating venous leg ulcers.
Nelson EA, Mani R, Thomas K, Vowden K.
School of Healthcare, University of Leeds, Baines Wing, Leeds, UK, LS2 9UT.
Update of:
Cochrane Database Syst Rev. 2008;(2):CD001899.
Abstract
BACKGROUND: Intermittent pneumatic compression (IPC) is a mechanical method of delivering
compression to swollen limbs that can be used to treat venous leg ulcers and limb swelling due to
lymphoedema.
OBJECTIVES: To determine whether IPC increases the healing of venous leg ulcers. To determine the
effects of IPC on health related quality of life of venous leg ulcer patients.
SEARCH STRATEGY: For this update we searched the Cochrane Wounds Group Specialised Register
(searched 10 December 2010); the Cochrane Central Register of Controlled Trials (CENTRAL) (The
Cochrane Library 2010, Issue 4); Ovid MEDLINE (2007 to November Week 3 2010); Ovid MEDLINE
(In-Process & Other Non-Indexed Citations December 09, 2010); Ovid EMBASE (2007 to 2010 Week
48); and EBSCO CINAHL (2007 to 3 December 2010).
SELECTION CRITERIA: We included randomised controlled trials (RCTs) that compared the effects of
IPC with control (sham IPC or no IPC) or made comparisons between IPC treatment regimens, in venous
ulcer management.
DATA COLLECTION AND ANALYSIS: Both review authors reviewed titles and abstracts and agreed
on full studies to be retrieved. One review author extracted data and assessed studies for risk of bias and
this was checked by a second review author.
MAIN RESULTS: We identified seven randomised controlled trials (including 367 people in total). Only
one trial was at low risk of bias having reported adequate randomisation, allocation concealment and blinded
outcome assessment. In one trial (80 people) more ulcers healed with IPC than with dressings (62% vs
28%; p=0.002). Four trials compared IPC plus compression with compression alone. The first of these
trials (45 people) found increased ulcer healing with IPC plus compression than with compression alone
(risk ratio for healing 11.4, 95% Confidence Interval 1.6 to 82). The remaining three trials (122 people)
found no evidence of a benefit for IPC plus compression compared with compression alone.One small trial
(16 people) found no difference between IPC (without additional compression) and compression bandages
alone. One trial (104 people) compared different ways of delivering IPC and found that rapid IPC healed
more ulcers than slow IPC (86% vs 61%).
AUTHORS' CONCLUSIONS: IPC may increase healing compared with no compression, but it is not
clear whether it increases healing when added to treatment with bandages, or if it can be used instead of
compression bandages. Rapid IPC was better than slow IPC in one trial. Further trials are required to
determine whether IPC increases the healing of venous leg ulcers when used in modern practice where
compression therapy is widely used.
PMID: 21328252 [PubMed - in process]
February 25, 2011
Int J Dermatol. 2011 Mar;50(3):310-34. doi: 10.1111/j.1365-4632.2010.04744.x.
Integrating modern dermatology and Ayurveda in the treatment of vitiligo and lymphedema in India.
Narahari SR, Ryan TJ, Bose KS, Prasanna KS, Aggithaya GM.
Department of Integrative Dermatology, Institute of Applied Dermatology, Kasaragod, India Department of
Dermatology, University of Oxford, Oxford, UK.
Abstract
Background Globally, governments have recognized the growing popularity of Complementary and
Alternative Medicines and the possibility of their combined use with biomedicine. Decisions within the
Government of India have led to a conducive environment for conducting clinical studies, to achieve
integration of more than one system of medicine, so that their combined benefits can be brought to bear on
chronic, difficult-to-treat conditions. Aim To develop integrative dermatology treatment protocols for
patients with long-standing skin diseases who have received treatment from many centers. Materials and
Methods A team of doctors from modern dermatology, Ayurveda, yoga therapy, and homeopathy studied
recruited patients to develop mutual orientation on each therapeutic system and a working knowledge of
approach to their clinical diagnosis. Six-hundred thirty-eight patients affected by lower limb lymphedema
requiring skin care as a major part of treatment were treated integrating modern dermatology and Ayurveda.
Three-hundred eighty-one vitiligo patients were examined and treated to understand the clinical
presentations and treatment options in Ayurveda. Results A two-step cluster analysis performed by SPSS
Version 16 showed average volume reductions of 13.3% and 23% on day 14, 19.7% and 31.1% on day
45, and 23.4% and 39.7% on day 90 of treatment in small and large lymphedematous limbs. Inflammatory
episodes before the onset on this treatment was reported by 79.5% of our lymphedema patients, and 9.4%
reported this at the end of three months after our treatment. Among vitiligo patients, we found that 39.6% of
patients had kapha, 39.8%pitta, 10.8% had vatha and 0.52% has tridoshaja presentation. There are over
100 treatment options available in Ayurveda to treat vitiligo. Discussion Each system of medicine recognizes
the same disease albeit with minor difference in description. Skin care procedures like washing and
emollients restore the barrier function and skin health. We have converged Ayurvedic skin care with that of
dermatology with an aim of achieving patient management that is better than that achievable by a single
system alone. Overload of the lymphatic system due to loss of epidermal barrier function and consequent
inflammation from bacteria and soil irritants is responsive to selected Ayurvedic herbal preparations.
Conclusion It is evident that integration at the therapeutic level is possible, although the pathological basis is
interpreted differently. Irrespective of background understanding of the given disease, a mutually oriented
multisystem therapeutic team was able to effectively use medicines from more than one system of medicine
and to develop guidelines for their prescription and a patient care algorithm.
© 2011 The International Society of Dermatology.
PMID: 21342165 [PubMed - in process]
Clin Med Insights Oncol. 2011 Feb 7;5:9-14.
Life after breast cancer: dealing with lymphoedema.
Cidón EU, Perea C, López-Lara F.
Medical Oncology Department, Clinical University Hospital of Valladolid, Spain.
Abstract
BACKGROUND: In recent years, breast cancer (BC) mortality rates have declined, reflecting advances in
early detection. Prevention and management of treatment sequelae that could impair function or quality of life
have increased in relevance. Lymphoedema after BC treatment is one of these sequelae. It is caused by an
acquired interruption or damage to the axillary lymphatic system and it is characterized by an abnormal
accumulation of fluids and other substances in the tissue.
PURPOSE: We observed a group of patients with incidents of BC aiming to estimate the lymphoedema
incidence, degree, time course, symptoms and treatment they received.
METHODS AND RESULTS: We evaluated 127 women. Median age was 58 years. 66% were
postmenopausal. The median number of axillary nodes was 9. Over the first five years of follow-up we were
informed about hand/arm swelling, thickness or tiredness by 37% of this group. The median of axillary nodes
affected by metastatic cells in our patients with lymphoedema was 6. The symptoms they referred to us as
the most relevant were heaviness (33%), tiredness (27%), jewelry or clothing too tight (25%), swelling and
indentations (9%) and difficulty writing (6%). Several of them had psychological problems.
CONCLUSION: We know of the relevance of lymphoedema in BC patients but its natural history and most
effective therapies are poorly understood. Self-reported symptoms are relevant to promptly start therapy.
PMID: 21339859 [PubMed - in process]
Am Surg. 2011 Feb;77(2):248-9.
Median, ulnar, and radial nerve entrapments in a patient with breast cancer after treatment for lymphedema.
Kara M, Ozçakar L, Malas FU, Kara G, Altundag K.
Hacettepe University Medical School, Ankara, Turkey.
PMID: 21337898 [PubMed - in process]
MEDNEWS DOCS:
February 22, 2011 - Three-Year Data From Phase 2 Trial Of Genzyme Gaucher Disease Oral Compound
Suggest Sustained Or Further Improvement Across All Endpoints –
Genzyme Corporation (NASDAQ: GENZ) announced three-year follow-up data from patients enrolled in
the phase 2 clinical trial for its investigational oral therapy for Gaucher disease type 1 known as eliglustat
tartrate. Sustained or further improvements were observed across all endpoints, including bone disease, at
the three-year timepoint. The results were presented for the first time this week at the Lysosomal Disease
Network WORLD Symposium in Las Vegas, Nevada.
Genzyme previously reported that the eliglustat tartrate phase 2 trial had met its primary endpoint at one
year, and that data demonstrated continued improvement through two years. The primary composite
endpoint was a clinically meaningful response in at least two of three endpoints: improvements in spleen size,
hemoglobin and platelet levels. The study has continued with 19 patients through three years. The extension
phase of this trial is still ongoing.
Eliglustat tartrate continued to show robust clinical response through three years:
- Spleen volume decreased from baseline by a mean of 61 percent and liver volume decreased from
baseline by 29 percent.
- Hemoglobin level increased from baseline by a mean of 2.6 grams per deciliter.
- Platelet count increased from baseline by a mean of 91 percent.
The study also analyzed the clinical response of patients in the phase 2 trial with respect to achieving
therapeutic goals. Due to the heterogeneity of Gaucher disease, therapeutic goals were previously developed
by experts involved in the treatment of Gaucher patients to assess their response to enzyme replacement
therapy (ERT). Most patients dosed with eliglustat tartrate met established therapeutic goals for hemoglobin,
platelets, spleen volume and liver volume, demonstrating progressive and clinically meaningful responses in
multiple organ systems. At three years, 100 percent of patients met at least 3 of the 4 therapeutic goals
developed for hematologic and organ volume parameters.
The three-year data also included analyses that suggest eliglustat tartrate positively impacts indicators of
bone disease through three years of follow up. These indicators include bone mineral density in the lumbar
spine, as measured by dual energy x-ray absorptiometry (DXA), and dark marrow signal in the femur, as
visualized by magnetic resonance imaging (MRI). Dark marrow reflects the infiltration of lipid-laden Gaucher
cells into bone marrow. Specifically:
- In the 18 patients at baseline with dark marrow in the femur visible by MRI, five improved by one year,
seven by two years and 10 by three years, with the other eight patients remaining stable.
- In the 15 patients with results available at all time points, bone mineral density in the lumbar spine showed
clinically and statistically significant improvements after one year of treatment (T score = +0.4) which further
improved after 2 years (T score = +0.6) and were sustained after three years of treatment.
Ravi S. Kamath, M.D., Ph.D., Staff Radiologist at Massachusetts General Hospital and Instructor in
Radiology at Harvard Medical School, who is the central radiology reviewer for the phase 2 study, said,
"These data suggest that eliglustat tartrate may have a meaningful clinical impact on bone disease in Gaucher
disease type 1 patients."
The most common adverse events (AEs) reported in greater than 2 patients through three years included
viral infections (six patients), urinary tract infections and upper respiratory infections (4 patients each),
headache, increased blood pressure, diarrhea and abdominal pain (three patients each). Eight drug-related
AEs, including one serious event, were reported in six patients. Most AEs overall and all drug-related AEs
were considered mild. The largest number of AEs was reported during the first 3 months of treatment.
"For thirty years, Genzyme has pioneered treatments for patients with lysosomal storage disorders, including
the very first enzyme replacement therapy for Gaucher disease," said Genzyme's President, Personalized
Genetic Health, John P. Butler. "Our momentum continues through the phase 3 trials - the largest ever
conducted for Gaucher - as we build upon our foundation and commitment to Gaucher and look to extend
the therapeutic options available to patients and physicians."
Eliglustat tartrate, a capsule taken orally, is being developed to provide a convenient treatment alternative for
adult patients with Gaucher disease type 1, and to offer a broader range of treatment options for patients
and physicians to achieve individual therapeutic goals. Genzyme is currently enrolling patients in three global,
multi-center, phase 3 trials of eliglustat tartrate. This is the largest clinical program ever focused on Gaucher
disease, with over 50 sites in more than 25 countries currently participating. Genzyme's Gaucher disease
portfolio also offers Cerezyme® (imiglucerase for injection), the standard of care for patients with Gaucher
disease type 1, which is administered through intravenous infusions.
About Gaucher disease
Gaucher disease is an inherited condition affecting fewer than 10,000 people worldwide. People with
Gaucher disease do not have enough of an enzyme, acid ß-glucosidase (glucocerebrosidase) that breaks
down a certain type of fat molecule. As a result, lipid engorged cells (called Gaucher cells) amass in different
parts of the body, primarily the spleen, liver and bone marrow. Accumulation of Gaucher cells may cause
spleen and liver enlargement, anemia, excessive bleeding and bruising, bone disease and a number of other
signs and symptoms. The most common form of Gaucher disease, type 1, does not typically affect the
nervous system and brain.
About eliglustat tartrate
Eliglustat tartrate, a novel glucosylceramide analog given orally, is designed to partially inhibit the enzyme
glucosylceramide synthase, which results in reduced production of glucosylceramide. Glucosylceramide is
the substance that builds up in the cells and tissues of people with Gaucher disease. In preclinical studies, the
molecule, developed with James A. Shayman, M.D. from the University of Michigan, has shown high
potency and specificity. Based on its mechanism of action, which is independent of genotype, eliglustat
tartrate may be a potential therapy for patients with Gaucher disease type 1. Initiation of the phase 2 and 3
studies of eliglustat tartrate in Gaucher disease followed completion of an extensive pre-clinical research
effort and a phase 1 program. Over 300 subjects have now been treated in nine separate studies.
The data from the phase 2 trials with eliglustat tartrate were previously published in the journal Blood and
the results can be found at the below references:
- Phase 2 data at the 1 year time point: Lukina et al. Blood, Aug 2010; Vol. 116: 893 - 899
- Phase 2 data at the 2 year time point: Lukina et al. Blood, Nov 2010; Vol 116: 4095 - 4098
Cerezyme important safety information
Approximately 15 percent of patients have developed IgG antibodies, and these patients have a higher risk
of hypersensitivity reaction. Therefore periodic monitoring is suggested; caution should be exercised in
patients with antibodies or prior symptoms of hypersensitivity. Symptoms suggestive of hypersensitivity
occurred in 6.6 percent of patients, and include anaphylactoid reaction, pruritus, flushing, urticaria,
angioedema, chest discomfort, dyspnea, coughing, cyanosis and hypotension. Reactions related to
Cerezyme administration have been reported in less than 15 percent of patients. Each of the following events
occurred in less than 2 percent of the total patient population. Reported adverse events include nausea,
vomiting, abdominal pain, diarrhea, rash, fatigue, headache, fever, dizziness, chills, backache, and
tachycardia. Adverse events associated with the route of administration include discomfort, pruritus, burning,
swelling or sterile abscess at the site of venipuncture.
Source:
Genzyme Corporation
February 24, 2011 - Spinal Fluid Proteins Distinguish Lyme Disease From Chronic Fatigue Syndrome –
Patients who suffer from Neurologic Post Treatment Lyme disease (nPTLS) and those with the Chronic
Fatigue Syndrome report similar symptoms. However unique proteins discovered in spinal fluid can
distinguish those two groups from one another and also from people in normal health, according to new
research conducted by a team led by Steven E. Schutzer, MD, of the University of Medicine and Dentistry
of New Jersey New Jersey Medical School, and Richard D. Smith, Ph.D., of Pacific Northwest National
Laboratory. This finding, published in the journal PLoS ONE (February 23, 2011), also suggests that both
conditions involve the central nervous system and that protein abnormalities in the central nervous system are
causes and/or effects of both conditions.
The investigators analyzed spinal fluid from three groups of people. One group consisted of 43 patients who
fulfilled the clinical criteria for Chronic Fatigue Syndrome (CFS). The second group consisted of 25 patients
who had been diagnosed with, and treated for, Lyme disease but did not completely recover. The third
group consisted of 11 healthy control subjects. "Spinal fluid is like a liquid window to the brain," says Dr.
Schutzer. By studying the spinal fluid, the research team hoped to find abnormalities that could be used as
markers of each condition and could lead to improvements in diagnosis and treatment.
Taking advantage of previously unavailable methods for detailed analysis of spinal fluid, the investigators
analyzed the fluid by means of high powered mass spectrometry and special protein separation techniques.
They found that each group had more than 2,500 detectable proteins. The research team discovered that
there were 1) 738 proteins that were identified only in CFS but not in either healthy normal controls or
patients with nPTLS; 2) 692 proteins found only in the nPTLS patients. Previously there had been no
available candidate biomarkers to distinguish between the two syndromes, nor even strong evidence that the
central nervous system is involved in those conditions.
This research represents the most comprehensive analysis of the complete spinal fluid proteome (collection
of proteins) to date for both Chronic Fatigue Syndrome and Neurologic Post Treatment Lyme disease
(nPTLS). Prior to this study, many scientists believed that CFS was an umbrella category that included
nPTLS. However these results call those previous suppositions into question,
According to Dr. Schutzer, spinal fluid proteins can likely be used as a marker of disease, and this study
provides a starting point for research in that area. "One next step will be to find the best biomarkers that will
give conclusive diagnostic results," he says. "In addition, if a protein pathway is found to influence either
disease, scientists could then develop treatments to target that particular pathway."
"Newer techniques that are being developed by the team will allow researchers to dig even deeper and get
more information for these and other neurologic diseases, says Dr. Smith. "These exciting findings are the tip
of our research iceberg"
Other authors included Thomas E. Angel, Tao Liu, Athena A. Schepmoes, Therese R. Clauss, Joshua N.
Adkins and David G. Camp II of PNNL; Bart K. Holland of UMDNJ-New Jersey Medical School; Jonas
Bergquist of Uppsala University in Sweden; P.K. Coyle of SUNY-Stony Brook; Brian A. Fallon of
Columbia University; Benjamin H. Natelson of UMDNJ, Beth Israel Medical Center and Albert Einstein
School of Medicine.
Funding sources included the National Institutes of Health, through NIAID, NIDA, NINDS, the National
Center for Research Resources, the Swedish Research Council, Uppsala Berzelii Technology Center for
Neurodiagnostics, SciLifeLab-Uppsala, Environmental Molecular Sciences Laboratory, Pacific Northwest
National Laboratory. Time for Lyme, Lyme Disease Association, and the Tami Fund.
Journal citation: Schutzer SE, Angel TE, Liu T, Schepmoes AA, Clauss TR, et al. (2011) Distinct
Cerebrospinal Fluid Proteomes Differentiate Post-Treatment Lyme Disease from Chronic Fatigue
Syndrome. PLoS ONE 6(2): e17287. doi:10.1371/journal.pone.0017287
Source: University of Medicine and Dentistry of New Jersey (UMDNJ)
February 25, 2011 - Seeking Out Sentinel Lymph Nodes Of Breast Cancer Patients Using Microbubbles
To Light The Way –
Researchers at the University of California, San Diego are developing nonsurgical methods for identifying
critical lymph nodes to help doctors determine courses of treatment for breast cancer patients. The "sentinel
lymph node" is routinely biopsied or removed and dissected to determine the likelihood that the cancer has
spread beyond the breast. Dr. Andrew Goodwin, a post doctoral fellow in the Department of
Nanoengineering in the UC San Diego Jacobs School of Engineering recently received a Breast Cancer
Postdoctoral Fellowship Award from the U.S. Department of Defense to use novel microbubbles to mark
and interrogate the sentinel lymph node by means of a simple ultrasound scan.
"Since analysis of tumor stage is important for all breast cancer patients, this work would be expected to
help many patients," explained Goodwin.
Cancer cells can detach from a primary tumor and enter the bloodstream by way of the lymph nodes. To
determine if the cancer is spreading to other parts of the body, surgeons will biopsy or remove the lymph
nodes to look for invading cells. Finding cancer cells in the lymph nodes often changes the course of
treatment in an effort to kill any cancer cells that have already spread beyond the breast. Removing just the
first, or sentinel, lymph node for analysis helps to reduce the likelihood of developing lymphedema, a painful,
long-term swelling at the area of dissection.
The benefits of sentinel lymph node dissection for breast cancer patients were underscored by research
findings recently published in The Journal of the American Medical Association.
However, identifying the correct lymph node to remove is not straightforward. Current methods require
injection of radioactive colloids, which tend to blur at the injection site, or blue dye, which leaches into
multiple nodes and can only be observed after opening up the patient. These "black box" methods provide
little information about the structure of the lymph nodes at the tumor site, and both require the patient to be
prepared for a surgery that may be unnecessary if the contrast administration is unsuccessful.
Ultrasound and Microbubbles
"I'm trying to develop a better way to mark the sentinel lymph node," says Goodwin. His approach involves
using ultrasound - high-frequency sound waves used in medical imaging applications such as prenatal
sonograms - and gas-filled microbubbles with fluorescent outer shells. These microbubbles capable of
loading large amounts of dye are described in a recent article in the journal Soft Matter by Goodwin and
coworkers.
If Goodwin's vision translates to the clinic, a physician would inject the fluorescent microbubbles into the
tumor and then use ultrasound to visualize the bubbles as they drain away from the tumor and into the lymph
nodes under the arm. Once the lymph nodes have been imaged and the sentinel lymph node identified, the
radiologist will turn up the power of the ultrasound beam - but just in the area surrounding the sentinel lymph
node. This will burst the microbubbles and release non-toxic fluorescent polymer that is designed to stick
specifically in the lymph nodes for extended periods, allowing both the doctor and patient to adequately
prepare for the lymph node dissection surgery.
For now, critical next steps include testing how the outer shell of the microbubbles interact with the lymph
node lining, as well as tests in animal models.
Goodwin's UC San Diego collaborators include his mentor Sadik Esener, Director of the NanoTumor
Center for Cancer Nanotechnology, and Professor of NanoEngineering and of Electrical and Computer
Engineering at the Jacobs School of Engineering, and Radiology Professor Robert Mattrey, M.D. from the
UCSD Moores Cancer Center. Last year, Dr. Goodwin also received a Pathway to Independence (K99)
Award in Cancer Nanotechnology from the National Institute of Health on his work related to designing
microbubbles for site-specific ultrasound imaging of malignant blood clots.
Source:
Daniel Kane
University of California - San Diego
February 25, 2011 - Researchers Identify New, More Effective Tool In Diagnosing Breast Cancer And
Melanoma In Sentinel Lymph Nodes –
Researchers say a new kind of tracing agent is more accurate than current methods in helping identify tumor-
draining sentinel lymph nodes in breast cancer and melanoma patients. That's the finding in a new study that
appears in the online version of the Annals of Surgical Oncology.
"This is an important finding for both physicians, and patients," says Stanley Leong, M.D., M.S., F.A.C.S.,
Chief of Cutaneous Surgery at California Pacific Medical Center and the lead author of the study. "We are
always trying to find better ways of identifying which lymph nodes are cancerous, this new approach does
just that with great accuracy, almost 90 percent of the time, and without any apparent safety issues."
Dr. Leong and his team used Lymphoseek, a radioactive tracing agent developed by Neoprobe, to see how
effective it was in mapping the spread of two solid tumor cancers breast and melanoma to surrounding or
sentinel lymph nodes, the first nodes to receive lymph drainage from a tumor.
Lymphoseek was injected into 78 patients (47 of them melanoma patients, 31 breast cancer patients) 55 of
whom then underwent imaging scans to map its movement through the lymph system. In more than 94
percent of these patients, Lymphoseek was able to identify a tumor draining lymph node before surgery.
In this Phase 2 trial Lymphoseek showed that it did not cause any reaction at the site of injection, reached
the targeted sentinel nodes faster than existing methods and was less likely to spread beyond the targeted
nodes to other more distant nodes.
Previous studies have shown that solid tumors, such as breast cancer and melanoma, use the lymphatic
system to spread to other parts of the body, including some regional sentinel nodes. Identifying how far
those tumors have spread and what nodes are affected can help identify how extensive the treatment needs
to be and can potentially limit the number of nodes that need to be removed.
"Our goal as surgeons is to remove only those nodes we need to and to avoid removing those not showing
any signs of cancer," says Dr. Leong. "Lymphoseek seems to be more accurate at giving us this information
than other mapping methods and that can hopefully help patients avoid unnecessary surgery."
Existing methods for mapping the spread of these tumors are relatively accurate but are all "off label" in that
they have not been approved by the Food and Drug Administration (FDA) for that use. Neoprobe is hoping
that this trial will enable it to move forward in applying for FDA approval for Lymphoseek as the first tracing
agent specifically radio-labeled for lymph node detection.
Source: California Pacific Medical Center
February 26, 2011 - Validation Of A Gene Expression To Distinguish Metastasizing From Non-
Metastasizing Head And Neck Cancers –
The validation of a test, based on gene expression and predicting the tumours that will metastasize in lymph
nodes of head & neck cancers, was presented today at the 3rd International Conference on innovative
approaches in Head and Neck Oncology (ICHNO), in Barcelona.
Dr Robert Takes, from the Radboud University Nijmegen Medical Centre, the Netherlands, reported results
of a study involving 222 cases of oral or oropharyngeal cancer. The study was jointly led by scientists from
Nijmegen and the University Medical Center Utrecht, and involved all eight head and neck oncological
centres of the Netherlands.
"Today, it is impossible with current diagnostic tools to detect small lymph node metastasis in patients with
head and neck squamous cell carcinoma and therefore it is common practice to operate on the neck even if
no metastases have been detected," said Dr Takes. "The majority of these operations is unnecessary
because, in most cases, no metastases are present."
If the chance of metastasis could be predicted more accurately, the number of operations could be reduced.
"In our study, determining gene expression changes in the primary tumour improved the distinction between
tumours that do metastasize from those that don't," continued Dr Takes.
With an array containing a set of 825 relevant genes, identified in a prior study and suitable for clinical
application, distinction between metastasizing and non-metastasizing tumours was possible. The test
correctly predicted the absence of metastasis in 89% of the cases.
"This is the first biological test that was able to obtain a high level of accuracy and has been validated in
multiple centres on a large cohort of patients," said Dr Takes.
"The possible reduction of unnecessary neck treatments in case of a negative test may result in decreased
morbidity without deterioration of oncological outcomes. Also, in the remaining cases that still develop
metastasis in the neck, salvage treatment is still possible," added Dr Takes.
This signature is an additional method to already existing means to assess the neck, like imaging techniques
and sentinel node procedures. "One important message arising from the study is that the combination of
biological (gene signature) and clinical factors did better than either alone," commented Prof Adrian Begg
from the Netherlands Cancer Institute (NKI). "It thus appears that this signature is a useful addition which
can help the decision on treatment policy."
"Treatment is usually mainly selected based on the anatomical extent of the primary tumour and its
metastasis. Additional biological information on the behaviour of each individual tumour could result in a
more tailored treatment resulting in better survival," said Dr Takes.
"Takes and colleagues have carried out an important and essential step in all studies on gene signatures,"
concluded Prof Begg, "namely to move on from the initial finding of potential prognostic or predictive
significance to validation in an independent clinical series."
"We look forward to further validation and refinement of this approach which opens promising
developments. In such studies it would still be useful to look at genome-wide expression, which would
provide the opportunity to not only validate the present signature but also to look for even better ones."
Source:
Cecile Hardon-Villard
European Society for Medical Oncology
Int J Gynecol Cancer. 2011 Feb;21(2):409-18.
Assessment of bilateral limb lymphedema by bioelectrical impedance spectroscopy.
Ward L, Winall A, Isenring E, Hills A, Czerniec S, Dylke E, Kilbreath S.
Abstract
OBJECTIVE: : The aim of the present study was to determine if the ratio of extracellular fluid (ECF),
including the lymph, to that of intracellular fluid (ICF), as measured by bioimpedance spectroscopy (BIS),
could be used to assess bilateral lymphedema (LE).
BACKGROUND: : The presence of LE is commonly determined as an increase in tissue volume due to the
presence of excess lymph relative to the volume of a comparable unaffected body region or to comparative
normative data. However, in bilateral LE of the limbs, a comparable body region, the contralateral limb, is
also affected, precluding normalization. An alternative is to normalize the increase in lymph volume, as ECF,
to that of ICF volume.
METHODS: : Extracellular/intracellular fluid ratios, expressed as the ratio of intracellular impedance (Ri) to
extracellular impedance (R0), for the limbs of 277 female and 224 male controls were determined from an
accumulated database of impedance data. Equivalent data were obtained for an opportunistic cross-
sectional sample of 37 female and 5 male participants with bilateral LE of the legs. The ratios of Ri/R0 in the
lymphedematous legs of the affected participants were compared with the equivalent ratios in the unaffected
arms of the same participants and with those of the controls using box plots and visualized as bivariate data
using tolerance ellipses.
RESULTS: : Despite Ri/R0 ratios varying with age, sex, and limb dominance, comparison of the ratio for
affected legs (normalized to the ratio in the unaffected arms) with equivalent ratios observed in a control
population (as bivariate tolerance plots) was capable of discriminating between 70% and 89% of the
participants with LE.
CONCLUSIONS: : Bioelectrical impedance spectroscopy and determination of Ri/R0 ratios as indices of
ECF/ICF ratios holds promise for the semiquantitative assessment of bilateral LE.
PMID: 21270623 [PubMed - in process]
Int J Gynecol Cancer. 2011 Feb;21(2):385-90.
A Retrospective Analysis of Postoperative Complications With or Without Para-aortic Lymphadenectomy
in Endometrial Cancer.
Konno Y, Todo Y, Minobe S, Kato H, Okamoto K, Sudo S, Takeda M, Watari H, Kaneuchi M, Sakuragi
N.
*Department of Obstetrics and Gynaecology, Hokkaido University School of Medicine, Sapporo, Japan;
and †Division of Gynecologic Oncology, National Hospital Organization, Hokkaido Cancer Center,
Sapporo, Japan.
Abstract
INTRODUCTION: : Although para-aortic lymphadenectomy (PALX) has not been accepted as a standard
treatment for patients with endometrial cancer, it is possible that systematic lymphadenectomy including
PALX has therapeutic significance for patients with intermediate-/high-risk endometrial cancer. On the other
hand, a consensus regarding the safety of PALX has not been reached. The aim of this study was to
compare the incidence rates of postoperative complications after pelvic lymphadenectomy (PLX) with or
without PALX in patients with uterine corpus cancer.
METHODS: : A retrospective chart review was carried out for all patients with endometrial cancer treated
at 2 tertiary centers between 1998 and 2004. Surgery at one institute included both PLX and PALX,
whereas PLX alone was routinely performed at the other institute. A total of 142 patients underwent PLX +
PALX and 138 patients underwent PLX alone. We evaluated postoperative complications including
intraoperative injury, ileus, lymphedema, lymphocyst, and thrombosis.
RESULTS: : There was no fatal accident associated with surgery. Lymphedema was the most frequent
complication. Comparing the PLX + PALX group and the PLX group, there were no significant differences
in the rate of cases of lymphedema (23.2% vs 28.3%), lymphocyst (9.2% vs 9.4%), and thrombosis (4.9%
vs 2.2%). The rate of cases of mild/moderate ileus in the PLX + PALX group was significantly higher than
that in the PLX group (10.5% vs 2.9%; P = 0.011). However, no significant difference in the rates of cases
of severe ileus was found between the 2 groups (1.4% vs 0.7%). There were also no significant differences
between the 2 groups in the rates of intraoperative organ injury (2.8% vs 2.2%) and secondary operation
for postoperative complications (4.9% vs 4.3%).
CONCLUSIONS: : Para-aortic lymphadenectomy can be performed with an acceptable morbidity under
the conditions in which it is performed by experienced surgeons, and measures to prevent complications are
properly taken.
PMID: 21270621 [PubMed - in process]
Eur J Surg Oncol. 2011 Mar;37(3):187-98. Epub 2011 Jan 26.
Positron emission tomography (PET) for assessment of axillary lymph node status in early breast cancer: A
systematic review and meta-analysis.
Cooper KL, Harnan S, Meng Y, Ward SE, Fitzgerald P, Papaioannou D, Wyld L, Ingram C, Wilkinson
ID, Lorenz E.
School of Health and Related Research (ScHARR), University of Sheffield, Regent Court, 30 Regent
Street, Sheffield S1 4DA, UK.
Abstract
PURPOSE: Sentinel lymph node biopsy (SLNB) and axillary lymph node dissection (ALND) are used to
assess axillary nodal status in breast cancer, but are invasive procedures associated with morbidity, including
lymphoedema. This systematic review evaluates the diagnostic accuracy of positron emission tomography
(PET), with or without computed tomography (CT), for assessment of axillary nodes in early breast cancer.
METHODS: Eleven databases including MEDLINE, EMBASE and the Cochrane Library, plus research
registers and conference proceedings, were searched in April 2009. Study quality was assessed using the
QUality Assessment of Diagnostic Accuracy Studies (QUADAS) checklist. Sensitivity and specificity were
meta-analysed using a bivariate random effects approach.
RESULTS: Across 26 studies evaluating PET or PET/CT (n = 2591 patients), mean sensitivity was 63%
(95% CI: 52-74%; range 20-100%) and mean specificity 94% (95% CI: 91-96%; range 75-100%).
Across 7 studies of PET/CT (n = 862), mean sensitivity was 56% (95% CI: 44-67%) and mean specificity
96% (90-99%). Across 19 studies of PET-only (n = 1729), mean sensitivity was 66% (50-79%) and mean
specificity 93% (89-96%). Mean sensitivity was 11% (5-22%) for micrometastases (=2 mm; five studies; n
= 63), and 57% (47-66%) for macrometastases (>2 mm; four studies; n = 111).
CONCLUSIONS: PET had lower sensitivity and specificity than SLNB. Therefore, replacing SLNB with
PET would avoid the adverse effects of SLNB, but lead to more false negative patients at risk of recurrence
and more false positive patients undergoing unnecessary ALND. The present evidence does not support the
routine use of PET or PET-CT for the assessment of the clinically negative axilla.
Crown Copyright © 2011. Published by Elsevier Ltd. All rights reserved.
PMID: 21269795 [PubMed - in process]
February 4, 2011
Circulation. 2011 Jan 31. [Epub ahead of print]
Growth Factor Therapy and Autologous Lymph Node Transfer in Lymphedema.
Lähteenvuo M, Honkonen K, Tervala T, Tammela T, Suominen E, Lähteenvuo J, Kholová I, Alitalo K, Ylä-
Herttuala S, Saaristo A.
Department of Biotechnology and Molecular Medicine, A.I. Virtanen Institute for Molecular Sciences,
University of Eastern Finland, Kuopio.
Abstract
Background- Lymphedema after surgery, infection, or radiation therapy is a common and often incurable
problem. Application of lymphangiogenic growth factors has been shown to induce lymphangiogenesis and
to reduce tissue edema. The therapeutic effect of autologous lymph node transfer combined with adenoviral
growth factor expression was evaluated in a newly established porcine model of limb lymphedema. Methods
and Results- The lymphatic vasculature was destroyed within a 3-cm radius around an inguinal lymph node.
Lymph node grafts and adenovirally (Ad) delivered vascular endothelial growth factor (VEGF)-C (n=5) or
VEGF-D (n=9) were used to reconstruct the lymphatic network in the inguinal area; AdLacZ (ß-
galactosidase; n=5) served as a control. Both growth factors induced robust growth of new lymphatic
vessels in the defect area, and postoperative lymphatic drainage was significantly improved in the VEGF-
C/D-treated pigs compared with controls. The structure of the transferred lymph nodes was best preserved
in the VEGF-C-treated pigs. Interestingly, VEGF-D transiently increased accumulation of seroma fluid in the
operated inguinal region postoperatively, whereas VEGF-C did not have this side effect. Conclusions-
These results show that growth factor gene therapy coupled with lymph node transfer can be used to repair
damaged lymphatic networks in a large animal model and provide a basis for future clinical trials of the
treatment of lymphedema.
PMID: 21282502 [PubMed - as supplied by publisher]
Clin J Oncol Nurs. 2011 Feb 1;15(1):99-101.
Cutaneous metastases in breast cancer.
Kalmykow B, Walker S.
Prostate Cancer Care Center, Beth Israel Deaconess Medical Center, Boston, MA.
Abstract
Cutaneous metastases occur more often in breast cancer than in other diseases in women. Presentation often
is ambiguous because the metastases can mimic other common processes (e.g., cellulitis, lymphedema).
Accurate differential diagnosis identifies less obvious manifestations of progressive disease and allows for
appropriate management. Although interventions are aimed at halting disease progression, cutaneous
metastases indicate an incurable diagnosis. Treatment focuses on delaying progressive disease, controlling
symptoms, and maintaining quality of life. The care of skin metastases evolves as the tumor spreads and
more tissue destruction occurs. Skin management and topical interventions increase comfort, decrease
distress, and create feelings of control in this population.
PMID: 21278046 [PubMed - in process]
Int J Surg. 2011 Jan 27. [Epub ahead of print]
Mathematical model to predict risk for lymphoedema after treatment of cutaneous melanoma.
Campanholi LL, Duprat Neto JP, Fregnani JH.
AC Camargo Hospital, São Paulo, Brazil.
Abstract
AIM: To evaluate risk factors for lymphoedema development in the upper and lower limbs and to propose a
model that predicts risk of lymphoedema after lymphadenectomy.
PATIENTS: We studied 84 patients who had undergone radical lymphadenectomies for cutaneous
melanoma from 1990 to 2008.
METHODS: The patients included underwent an evaluation that consisted of measurement of limb volume
using perimetry, application of the manually acquired perimetric data to the truncated-cone formula, and data
from medical records.
RESULTS: Using multivariate analysis, we obtained the following risk factors for the development of
lymphoedema: reconstruction with graft (p=0.013), Breslow depth >4mm (p=0.029), ilioinguinal
lymphadenectomy (p=0.037) and wound infection (p=0.036). We assigned points to each factor as dictated
by the value of the regression coefficient, as follows: infection (1 point), ilioinguinal lymphadenectomy and
Breslow >4mm (2 points each) and reconstruction with graft (3 points). The mathematical model for
predicting lymphoedema risk in the limb ipsilateral to the lymphadenectomy was based on risk groups,
defined by score: low risk=0 point (for which we calculated an 8.3% chance of developing lymphoedema),
intermediate risk=1-2 points (26.8%), high risk=3 points (52.9%) and very high risk=4 or more points
(88.9%).
CONCLUSIONS: This study identified a melanoma thickness >4mm, graft reconstruction, ilioinguinal
lymphadenectomy and infection as risk factors for lymphoedema. From these factors, we constructed a
mathematical model that successfully predicted risk of post-lymphadenectomy lymphoedema. The combined
presence of these risk factors increased the chance of developing lymphoedema.
Copyright © 2011 Surgical Associates Ltd. Published by Elsevier Ltd. All rights reserved.
PMID: 21276878 [PubMed - as supplied by publisher]
Health Technol Assess. 2011 Jan;15(4):1-134.
Positron emission tomography (PET) and magnetic resonance imaging (MRI) for the assessment of axillary
lymph node metastases in early breast cancer: systematic review and economic evaluation.
Cooper K, Meng Y, Harnan S, Ward S, Fitzgerald P, Papaioannou D, Wyld L, Ingram C, Wilkinson I,
Lorenz E.
School of Health and Related Research (ScHARR), University of Sheffield, Sheffield, UK.
Abstract
BACKGROUND: Breast cancer is the most common type of cancer in women. Evaluation of axillary lymph
node metastases is important for breast cancer staging and treatment planning.
OBJECTIVES: To evaluate the diagnostic accuracy, cost-effectiveness and effect on patient outcomes of
positron emission tomography (PET), with or without computed tomography (CT), and magnetic resonance
imaging (MRI) in the evaluation of axillary lymph node metastases in patients with newly diagnosed early-
stage breast cancer.
DATA SOURCES: A systematic review of literature and an economic evaluation were carried out. Key
databases (including MEDLINE, EMBASE and nine others) plus research registers and conference
proceedings were searched for relevant studies up to April 2009. A decision-analytical model was
developed to determine cost-effectiveness in the UK.
REVIEW METHODS: One reviewer assessed titles and abstracts of studies identified by the search
strategy, obtained the full text of relevant papers and screened them against inclusion criteria. Data from
included studies were extracted by one reviewer using a standardised data extraction form and checked by
a second reviewer. Discrepancies were resolved by discussion. Quality of included studies was assessed
using the quality assessment of diagnostic accuracy studies (QUADAS) checklist, applied by one reviewer
and checked by a second.
RESULTS: Forty-five citations relating to 35 studies were included in the clinical effectiveness review: 26
studies of PET and nine studies of MRI. Two studies were included in the cost-effectiveness review: one of
PET and one of MRI. Of the seven studies evaluating PET/CT (n = 862), the mean sensitivity was 56%
[95% confidence interval (CI) 44% to 67%] and mean specificity 96% (95% CI 90% to 99%). Of the 19
studies evaluating PET only (n = 1729), the mean sensitivity was 66% (95% CI 50% to 79%) and mean
specificity 93% (95% CI 89% to 96%). PET performed less well for small metastases; the mean sensitivity
was 11% (95% CI 5% to 22%) for micrometastases (= 2 mm; five studies; n = 63), and 57% (95% CI
47% to 66%) for macrometastases (> 2 mm; four studies; n = 111). The smallest metastatic nodes detected
by PET measured 3 mm, while PET failed to detect some nodes measuring > 15 mm. Studies in which all
patients were clinically node negative showed a trend towards lower sensitivity of PET compared with
studies with a mixed population. Across five studies evaluating ultrasmall super-paramagnetic iron oxide
(USPIO)-enhanced MRI (n = 93), the mean sensitivity was 98% (95% CI 61% to 100%) and mean
specificity 96% (95% CI 72% to 100%). Across three studies of gadolinium-enhanced MRI (n = 187), the
mean sensitivity was 88% (95% CI 78% to 94%) and mean specificity 73% (95% CI 63% to 81%). In the
single study of in vivo proton magnetic resonance spectroscopy (n = 27), the sensitivity was 65% (95% CI
38% to 86%) and specificity 100% (95% CI 69% to 100%). USPIO-enhanced MRI showed a trend
towards higher sensitivity and specificity than gadolinium-enhanced MRI. Results of the decision modelling
suggest that the MRI replacement strategy is the most cost-effective strategy and dominates the baseline 4-
node sampling (4-NS) and sentinel lymph node biopsy (SLNB) strategies in most sensitivity analyses
undertaken. The PET replacement strategy is not as robust as the MRI replacement strategy, as its cost-
effectiveness is significantly affected by the utility decrement for lymphoedema and the probability of relapse
for false-negative (FN) patients.
LIMITATIONS: No included studies directly compared PET and MRI.
CONCLUSIONS: Studies demonstrated that PET and MRI have lower sensitivity and specificity than
SLNB and 4-NS but are associated with fewer adverse events. Included studies indicated a significantly
higher mean sensitivity for MRI than for PET, with USPIO-enhanced MRI providing the highest sensitivity.
However, sensitivity and specificity of PET and MRI varied widely between studies, and MRI studies were
relatively small and varied in their methods; therefore, results should be interpreted with caution. Decision
modelling based on these results suggests that the most cost-effective strategy may be MRI rather than
SLNB or 4-NS. This strategy reduces costs and increases quality-adjusted life-years (QALYs) because
there are fewer adverse events for the majority of patients. However, this strategy leads to more FN cases
at higher risk of cancer recurrence and more false- positive (FP) cases who would undergo unnecessary
axillary lymph node dissection. Adding MRI prior to SLNB or 4-NS has little effect on QALYs, though this
analysis is limited by lack of available data. Future research should include large, well-conducted studies of
MRI, particularly using USPIO; data on the long-term impacts of lymphoedema on cost and patient utility;
studies of the comparative effectiveness and cost-effectiveness of SLNB and 4-NS; and more robust UK
cost data for 4-NS and SLNB as well as the cost of MRI and PET techniques.
FUNDING: This study was funded by the Health Technology Assessment programme of the National
Institute of Health Research.
PMID: 21276372 [PubMed - in process]
Int Angiol. 2010 Oct;29(5):391-470.
Compression therapy. Proceedings of a meeting organized by the International Compression Club.
September 2008.
Lucca, Italy.
[No authors listed]
PMID: 21275106 [PubMed - indexed for MEDLINE]
February 9, 2011
J Cutan Med Surg. 2011 Jan-Feb;15(1):61-2.
An approach to the treatment of vulvar lymphedema.
Bourgeault E, Giroux L.
PMID: 21291658 [PubMed - in process]
Dermatological and soft-tissue manifestations of Fabry disease: characteristics and response to enzyme
replacement therapy.
Lidove O, Jaussaud R, Aractingi S.
In: Mehta A, Beck M, Sunder-Plassmann G, editors. Fabry Disease: Perspectives from 5 Years of FOS.
Oxford: Oxford PharmaGenesis; 2006. Chapter 24.
Excerpt
Early manifestations of Fabry disease include dermatological and soft-tissue symptoms, such as
angiokeratomas, acroparaesthesia, abnormal sweating (hypohidrosis and hyperhidrosis) and lymphoedema.
Recognition of these symptoms is vital for the early diagnosis and treatment of Fabry disease. It is therefore
important that dermatologists, as well as other specialists, are aware of the manifestations of Fabry disease.
Clinical studies and data from FOS – the Fabry Outcome Survey – have suggested that enzyme replacement
therapy with agalsidase alfa can improve sweating, heat intolerance and pain in patients with Fabry disease.
Copyright © 2006, Oxford PharmaGenesis™
Sections
Introduction
Pathology of cutaneous lesions in Fabry disease
Sweating
Lymphoedema
Acroparaesthesia
Facial dysmorphia
Response to ERT
Conclusions
References
PMID: 21290701 [PubMed]
February 11, 2011
ANZ J Surg. 2011 Jan;81(1-2):103-4. doi: 10.1111/j.1445-2197.2010.05625.x.
Massive localized lymphoedema.
Jones M, Marshall D, Mason D.
Anaesthetics Department, South Devon Healthcare NHS Foundation Trust, Torquay, Devon, UK.
PMID: 21299819 [PubMed - in process]
MED NEWS DOCUMENT FORMATTED:
February 10, 2011
Photodynamic Ablation Of Lymphatic Vessels And Intralymphatic Cancer Cells Prevents Metastasis
Tumor cells have several routes that enable them to move from the primary tumor to distant tissues, a
process called metastasis. It is metastasis of the primary tumor that kills most cancer patients. One of the
least studied routes of metastasis is the lymphatic system. Many tumors produce factors that promote the
formation of new lymphatic vessels (lymphangiogenesis). The newly formed lymphatic vessels enable tumor
cells to travel from the primary tumor to the regional lymph nodes from whence they can spread throughout
the body.
Current treatment practice is to surgically remove the primary tumor as well as the metastatic lymph nodes,
but tumor cells in metastatic transit inside the lymphatic vessels had not been given much attention.
In a new study, Dr Tuomas Tammela and colleagues at the University of Helsinki, Finland, investigated
whether eradicating tumor-associated lymphatic vessels and the tumor cells they contain using photodynamic
therapy (PDT) with a light-activated cytotoxic drug could reduce or eliminate tumor metastasis. They
selected the mouse ear as their model system because it is easy to image both the lymphatic vessels and the
in-transit tumor cells.
The researchers implanted mouse melanoma cells or human lung tumor cells into the mouse ear tip and
waited two weeks for the primary tumors to become established and to induce lymphangiogenesis. Using
deep-tissue microscopy, they observed that the newly formed lymphatic vessels contained in-transit tumor
cells as well as small tumor nodules. Using pathology sections taken from a patient with recurrent melanoma,
they confirmed that the tumor-associated lymphatic vessels of cancer patients contain in-transit tumor cells
and tumor nodules.
However, could PDT eliminate both tumor-associated lymphatic vessels and the tumor cells inside them?
The researchers injected verteporfin in a liposomal preparation intradermally into the mouse ear and showed
that this cytotoxic dye accumulated specifically in the lymphatic vessels. When they illuminated the mouse ear
with infrared laser light, the lymphatic vessels started to shrink and fragment, and became leaky. Also, the
researchers found that the mice receiving PDT and surgery had a much lower relapse rate than those that
underwent surgery alone.
Using a pig model, the researchers also showed that PDT can target lymphatic vessels deep within the body
and, thus, PDT could be useful eradicating tumor-associated lymphatic vessels deep within the tissues of
human cancer patients.
"These findings are new and exciting, because the cells in metastatic transit in tumor-draining lymphatic
vessels have not been given much attention previously", Dr. Tammela says.
"We do not expect PDT to replace current surgical techniques, which comprise removal of the primary
tumor and metastatic lymph nodes. However, PDT could easily be combined with existing surgical
techniques to destroy the lymphatic vessels draining from the tumor, as well as the tumor cell aggregates
residing within them."
PDT using verteporfin is currently used clinically to destroy overgrown blood vessels in the retina of patients
with macular degeneration. As both the drug and the PDT concept are already in use in patients, they are
more likely to receive regulatory approval for targeting tumor-associated lymphatic vessels in cancer patients
undergoing surgery than drugs still in earlier phases of development, Tammela states.
Source:
Dr. Tuomas Tammela
University of Helsinki
February 23, 2011 - Myofascial Release effective for many physical conditions - Coeur d'Alene Press – By
VIRGINIA TAFT –
Myofascial Release is used to treat acute pain due to accident or injury as well as chronic neck, back, sciatic
pain. It is also used to treat arthritis, Fibromyalgia, sciatica, TMJ, post surgical scar and lymphedema, just to
name a few. Myofascial Release or "MFR" is a very effective hands-on technique that provides sustained
pressure into myofascial restrictions to eliminate pain and restore motion.
It also allows the body to move to release holding patterns.
To understand this technique it is important to understand the fascial system. Myo, means muscle, and fascia
(pronounced "fasha") is the connective tissue. The fascia is a specialized system of the body that has an
appearance similar to a spider's web or a sweater. Fascia is very densely woven, covering and
interpenetrating every muscle, bone, nerve, artery and vein as well as all of our internal organs including
heart, lungs, brain ad spinal cord.
The most interesting aspect of the fascial system is that it is not just a system of separate coverings. It is
actually one structure that exists from head to foot without interruption. In this way, you can begin to see that
each part of the entire body is connected to every other part by the fascia, like the yarn in a sweater.
Fascia also plays an important role in the support of our bodies, since it surrounds and attaches to all
structures. These structures would not be able to provide stability without the constant pull of the fascial
system. In fact, our bones can be thought of as tent poles, which cannot support the structure without the
constant support of the guide wires (or fascia) to keep an adequate amount of tension to allow the tent (or
body) to remain upright with proper equilibrium.
Trauma, such as a fall, whiplash or surgery can cause tight areas in the fascia. This system is also affected by
repetitive motions or just habitual poor posture over time, which have a cumulative effect. The changes
caused in the fascial system influence the skeletal framework for our posture. The fascia can exert excessive
pressure producing pain or restriction of motion, decreased flexibility and is a determining factor in our ability
to withstand stress and strain.
Myofascial Release is a gentle, safe and highly effective, whole body, "hands on" approach. It allows us to
look at each patient as unique with focus on the whole body rather than just the injured part.
Often where we feel pain, is not where the problem really is located. MFR utilizes varying pressure from
heavy to light to eliminate pain and restore motion as well as deepens the relaxation response.
Patients may be seen one-on-one with a therapist or may opt for co-treatments with two therapists.
During these hands-on treatments therapists use may use other manual techniques and movement therapy.
The patient is an active participant in the treatment program. Each patient is given a home program to
maximize benefit from therapy. This promotes independence though education in proper body mechanics,
enhancement of strength, flexibility, as well as postural and movement awareness.
Coeur d' Alene Hand Therapy and Healing Center specializes in Advanced Myofascial Release and manual
therapy techniques. Call (208) 664-2901 for more information or to receive a free consultation
February 19, 2011
Am J Dermatopathol. 2011 Feb 1. [Epub ahead of print]
Lymphangiectases Are Common Underlying Warts and in Normal Peritumoral Skin: Histologic Evidence of
Decreased Immune Surveillance.
Paul J, Carlson JA.
From the Divisions of Dermatopathology and Dermatology, Department of Pathology, Albany Medical
Center, Albany, NY.
Abstract
BACKGROUND: Lymphangiectases are a histologic sign of lymphostasis, which is associated with
decreased immune cell trafficking and cell-mediated immunity.
OBJECTIVE: To determine if latent lymphedema is apparent underlying warts and in skin affected by
cutaneous neoplasia.
MATERIALS AND METHODS: The number and maximal dilation of lymphangiectases were measured in
the upper half of the dermis of 51 consecutive biopsies of warts, 230 consecutive normal skin samples from
primary skin tumor excisions, and 14 normal skin samples from breast reduction (11) and panniculectomy
(3) specimens.
RESULTS: All warts had one or more underlying lymphangiectases compared with 79% of peritumor
normal skin samples and 50% of cosmetic specimens. The mean number of lymphangiectases and mean
maximal dilation were significantly greater in warts than in peritumor skin, which was significantly greater than
cosmetic skin samples (3.6 vs. 1.3 vs. 0.12 lymphangiectases per square millimeter and 54 vs. 23 vs. 1 µm,
respectively; P = 0.0001). Warts exhibited mild fibrosis significantly more frequently than peritumor skin
(57% vs. 5%; P = 0.0001). For peritumor (normal) skin, age, solar elastosis, and adjacent malignancy
correlated with greater dilation of lymphatics. Solar elastosis also correlated with increased number of
lymphangiectases.
CONCLUSIONS: Minor trauma and solar elastosis from chronic ultraviolet radiation exposure are likely
the etiologic factors in the development of lymphostasis. By decreasing immune surveillance, latent
lymphedema ostensibly facilitates human papillomavirus infection and carcinogenesis.
PMID: 21317613 [PubMed - as supplied by publisher]
Cesk Patol. 2010 Oct;46(4):98-103.
[Lymphatic system: morphology and pathology update].
[Article in Czech]
Kholová I.
Pathology, Laboratory Centre, Tampere University Hospital, Tampere, Finland. ivana.kholova@sll.fimnet.fi
Abstract
The lymphatic system is crucial for the maintenance of tissue fluid balance, immune surveillance, and fatty
acids absorption in the intestine. The lymphatic vessels are also involved in the pathogenesis of tumor
metastasis, lymphedema, and various inflammatory processes. Recently, several markers specific for
lymphatic endothelium were found. Progress in the field of lymphatic growth factors and their receptors, and
molecular lymphatic biology has helped to understand better the lymphatic vasculature. This review
summarizes the updates on lymphatic system research and possible applications in routine pathological
diagnostics.
PMID: 21313736 [PubMed - in process]
February 22, 2011
Adv Ther. 2011 Feb 14. [Epub ahead of print]
Merino wool graduated compression stocking increases lower limb venous blood flow: A randomized
controlled trial.
Charles T, Mackintosh D, Healy B, Perrin K, Weatherall M, Beasley R.
Medical Research Institute of New Zealand, Private Bag 7902, Wellington, 6242, New Zealand, Thom.
Charles@mrinz.ac.nz.
Abstract
INTRODUCTION: Graduated compression stockings represent a nonpharmacological approach to reduce
the risk of deep vein thrombosis (DVT) and pulmonary embolism (PE) due to prolonged immobility through
reducing lower limb venous stasis. A novel merino wool, double-layer, below-knee graduated compression
stocking has been developed to reduce the risk of air travel-related DVT and PE.
METHODS: Twenty healthy adult participants were randomized to wear the novel graduated compression
stocking on either the left or right leg. Doppler ultrasound measurements of popliteal venous blood flow
were made on both legs over a 120-minute period. The primary outcome was peak systolic velocity in the
popliteal vein at 120 minutes. Secondary outcomes included mean flow velocity, total volume flow, vein
cross-sectional area, and change in ankle and calf measurements.
RESULTS: The popliteal vein peak systolic velocity was 0.35 cm/s (95% confidence intervals [CI], 0.22 to
0.49, P<0.001) higher with stocking use at 120 minutes, a difference of 24%. Mean flow velocity and total
volume flow were also significantly higher with stocking use. Ankle and calf circumference were decreased
with stocking use, with an overall difference of -6.3 mm (95% CI, -11.3 to -1.2, P=0.021) and -7.9 mm
(95% CI, -13.3 to -2.4, P=0.011), respectively.
CONCLUSION: The novel merino wool double-layer, below-knee graduated compression stocking
increases lower limb venous blood flow during prolonged seated immobility. Its use is likely to reduce the
risk of DVT and PE in situations of prolonged seated immobility, such as long-distance air travel. The
reduction in lower limb swelling associated with their use suggests that the stockings are likely to have utility
in the treatment of chronic venous insufficiency and lymphedema.
PMID: 21331557 [PubMed - as supplied by publisher]
Breast Cancer. 2011 Feb 18. [Epub ahead of print]
Lymphedema and breast cancer: a review of the literature.
Michael S, Charikleia S, Konstantinos K.
4th Department of Surgery, Medical School, Attikon General Hospital, University of Athens, Athens,
Greece, mixalislak@gmail.com.
Abstract
Breast cancer continues to be the most common malignancy among women in the United States. Despite its
high incidence, early detection and modern treatment have made long-term survival more common. One of
the most important sequelae of the treatment of breast cancer is the development of lymphedema. There are
many issues for women to deal with after treatment for breast cancer. Focusing on the quality of life after
breast cancer means dealing with issues such as an altered body image, changes in relationships with partner
and children, living with any ongoing side effects, and the fear of tumor recurrence. The objective of this
paper is to elucidate these issues concerning lymphedema.
PMID: 21331463 [PubMed - as supplied by publisher]
Scand J Urol Nephrol. 2011 Feb 18. [Epub ahead of print]
Management of diuretic treatment: A challenge in the obese patient.
Lassen CK, Jespersen B.
Department of Nephrology, Aarhus University Hospital, Skejby, Brendstrupgårdsvej 100, DK-8200
Aarhus N, Skejby, Denmark.
Abstract
Abstract The obesity epidemic is a major health concern. The diagnosis of acute illness and fluid imbalance
in the obese patient is complicated by a wide range of comorbidities such as cardiovascular disease, obesity
hypoventilation syndrome, non-alcoholic steatohepatitis and lymphoedema. Thus, obesity warrants
particularly careful clinical and biochemical assessment owing to its resemblance to fluid retention. Dosing of
diuretics is difficult in these patients. The blood urea:creatinine ratio should be widely used to detect
emerging cardiovascular and renal complications. This report presents an obese patient with congestive heart
failure due to a myocardial infarction, who subsequently was overdosed with diuretics. His prerenal acute
renal failure resolved when diuretics were stopped and the high urea:creatinine ratio was diagnostic.
PMID: 21329483 [PubMed - as supplied by publisher]
Cochrane Database Syst Rev. 2011 Feb 16;2:CD001899.
Intermittent pneumatic compression for treating venous leg ulcers.
Nelson EA, Mani R, Thomas K, Vowden K.
School of Healthcare, University of Leeds, Baines Wing, Leeds, UK, LS2 9UT.
Update of:
Cochrane Database Syst Rev. 2008;(2):CD001899.
Abstract
BACKGROUND: Intermittent pneumatic compression (IPC) is a mechanical method of delivering
compression to swollen limbs that can be used to treat venous leg ulcers and limb swelling due to
lymphoedema.
OBJECTIVES: To determine whether IPC increases the healing of venous leg ulcers. To determine the
effects of IPC on health related quality of life of venous leg ulcer patients.
SEARCH STRATEGY: For this update we searched the Cochrane Wounds Group Specialised Register
(searched 10 December 2010); the Cochrane Central Register of Controlled Trials (CENTRAL) (The
Cochrane Library 2010, Issue 4); Ovid MEDLINE (2007 to November Week 3 2010); Ovid MEDLINE
(In-Process & Other Non-Indexed Citations December 09, 2010); Ovid EMBASE (2007 to 2010 Week
48); and EBSCO CINAHL (2007 to 3 December 2010).
SELECTION CRITERIA: We included randomised controlled trials (RCTs) that compared the effects of
IPC with control (sham IPC or no IPC) or made comparisons between IPC treatment regimens, in venous
ulcer management.
DATA COLLECTION AND ANALYSIS: Both review authors reviewed titles and abstracts and agreed
on full studies to be retrieved. One review author extracted data and assessed studies for risk of bias and
this was checked by a second review author.
MAIN RESULTS: We identified seven randomised controlled trials (including 367 people in total). Only
one trial was at low risk of bias having reported adequate randomisation, allocation concealment and blinded
outcome assessment. In one trial (80 people) more ulcers healed with IPC than with dressings (62% vs
28%; p=0.002). Four trials compared IPC plus compression with compression alone. The first of these
trials (45 people) found increased ulcer healing with IPC plus compression than with compression alone
(risk ratio for healing 11.4, 95% Confidence Interval 1.6 to 82). The remaining three trials (122 people)
found no evidence of a benefit for IPC plus compression compared with compression alone.One small trial
(16 people) found no difference between IPC (without additional compression) and compression bandages
alone. One trial (104 people) compared different ways of delivering IPC and found that rapid IPC healed
more ulcers than slow IPC (86% vs 61%).
AUTHORS' CONCLUSIONS: IPC may increase healing compared with no compression, but it is not
clear whether it increases healing when added to treatment with bandages, or if it can be used instead of
compression bandages. Rapid IPC was better than slow IPC in one trial. Further trials are required to
determine whether IPC increases the healing of venous leg ulcers when used in modern practice where
compression therapy is widely used.
PMID: 21328252 [PubMed - in process]
February 25, 2011
Int J Dermatol. 2011 Mar;50(3):310-34. doi: 10.1111/j.1365-4632.2010.04744.x.
Integrating modern dermatology and Ayurveda in the treatment of vitiligo and lymphedema in India.
Narahari SR, Ryan TJ, Bose KS, Prasanna KS, Aggithaya GM.
Department of Integrative Dermatology, Institute of Applied Dermatology, Kasaragod, India Department of
Dermatology, University of Oxford, Oxford, UK.
Abstract
Background Globally, governments have recognized the growing popularity of Complementary and
Alternative Medicines and the possibility of their combined use with biomedicine. Decisions within the
Government of India have led to a conducive environment for conducting clinical studies, to achieve
integration of more than one system of medicine, so that their combined benefits can be brought to bear on
chronic, difficult-to-treat conditions. Aim To develop integrative dermatology treatment protocols for
patients with long-standing skin diseases who have received treatment from many centers. Materials and
Methods A team of doctors from modern dermatology, Ayurveda, yoga therapy, and homeopathy studied
recruited patients to develop mutual orientation on each therapeutic system and a working knowledge of
approach to their clinical diagnosis. Six-hundred thirty-eight patients affected by lower limb lymphedema
requiring skin care as a major part of treatment were treated integrating modern dermatology and Ayurveda.
Three-hundred eighty-one vitiligo patients were examined and treated to understand the clinical
presentations and treatment options in Ayurveda. Results A two-step cluster analysis performed by SPSS
Version 16 showed average volume reductions of 13.3% and 23% on day 14, 19.7% and 31.1% on day
45, and 23.4% and 39.7% on day 90 of treatment in small and large lymphedematous limbs. Inflammatory
episodes before the onset on this treatment was reported by 79.5% of our lymphedema patients, and 9.4%
reported this at the end of three months after our treatment. Among vitiligo patients, we found that 39.6% of
patients had kapha, 39.8%pitta, 10.8% had vatha and 0.52% has tridoshaja presentation. There are over
100 treatment options available in Ayurveda to treat vitiligo. Discussion Each system of medicine recognizes
the same disease albeit with minor difference in description. Skin care procedures like washing and
emollients restore the barrier function and skin health. We have converged Ayurvedic skin care with that of
dermatology with an aim of achieving patient management that is better than that achievable by a single
system alone. Overload of the lymphatic system due to loss of epidermal barrier function and consequent
inflammation from bacteria and soil irritants is responsive to selected Ayurvedic herbal preparations.
Conclusion It is evident that integration at the therapeutic level is possible, although the pathological basis is
interpreted differently. Irrespective of background understanding of the given disease, a mutually oriented
multisystem therapeutic team was able to effectively use medicines from more than one system of medicine
and to develop guidelines for their prescription and a patient care algorithm.
© 2011 The International Society of Dermatology.
PMID: 21342165 [PubMed - in process]
Clin Med Insights Oncol. 2011 Feb 7;5:9-14.
Life after breast cancer: dealing with lymphoedema.
Cidón EU, Perea C, López-Lara F.
Medical Oncology Department, Clinical University Hospital of Valladolid, Spain.
Abstract
BACKGROUND: In recent years, breast cancer (BC) mortality rates have declined, reflecting advances in
early detection. Prevention and management of treatment sequelae that could impair function or quality of life
have increased in relevance. Lymphoedema after BC treatment is one of these sequelae. It is caused by an
acquired interruption or damage to the axillary lymphatic system and it is characterized by an abnormal
accumulation of fluids and other substances in the tissue.
PURPOSE: We observed a group of patients with incidents of BC aiming to estimate the lymphoedema
incidence, degree, time course, symptoms and treatment they received.
METHODS AND RESULTS: We evaluated 127 women. Median age was 58 years. 66% were
postmenopausal. The median number of axillary nodes was 9. Over the first five years of follow-up we were
informed about hand/arm swelling, thickness or tiredness by 37% of this group. The median of axillary nodes
affected by metastatic cells in our patients with lymphoedema was 6. The symptoms they referred to us as
the most relevant were heaviness (33%), tiredness (27%), jewelry or clothing too tight (25%), swelling and
indentations (9%) and difficulty writing (6%). Several of them had psychological problems.
CONCLUSION: We know of the relevance of lymphoedema in BC patients but its natural history and most
effective therapies are poorly understood. Self-reported symptoms are relevant to promptly start therapy.
PMID: 21339859 [PubMed - in process]
Am Surg. 2011 Feb;77(2):248-9.
Median, ulnar, and radial nerve entrapments in a patient with breast cancer after treatment for lymphedema.
Kara M, Ozçakar L, Malas FU, Kara G, Altundag K.
Hacettepe University Medical School, Ankara, Turkey.
PMID: 21337898 [PubMed - in process]
MEDNEWS DOCS:
February 22, 2011 - Three-Year Data From Phase 2 Trial Of Genzyme Gaucher Disease Oral Compound
Suggest Sustained Or Further Improvement Across All Endpoints –
Genzyme Corporation (NASDAQ: GENZ) announced three-year follow-up data from patients enrolled in
the phase 2 clinical trial for its investigational oral therapy for Gaucher disease type 1 known as eliglustat
tartrate. Sustained or further improvements were observed across all endpoints, including bone disease, at
the three-year timepoint. The results were presented for the first time this week at the Lysosomal Disease
Network WORLD Symposium in Las Vegas, Nevada.
Genzyme previously reported that the eliglustat tartrate phase 2 trial had met its primary endpoint at one
year, and that data demonstrated continued improvement through two years. The primary composite
endpoint was a clinically meaningful response in at least two of three endpoints: improvements in spleen size,
hemoglobin and platelet levels. The study has continued with 19 patients through three years. The extension
phase of this trial is still ongoing.
Eliglustat tartrate continued to show robust clinical response through three years:
- Spleen volume decreased from baseline by a mean of 61 percent and liver volume decreased from
baseline by 29 percent.
- Hemoglobin level increased from baseline by a mean of 2.6 grams per deciliter.
- Platelet count increased from baseline by a mean of 91 percent.
The study also analyzed the clinical response of patients in the phase 2 trial with respect to achieving
therapeutic goals. Due to the heterogeneity of Gaucher disease, therapeutic goals were previously developed
by experts involved in the treatment of Gaucher patients to assess their response to enzyme replacement
therapy (ERT). Most patients dosed with eliglustat tartrate met established therapeutic goals for hemoglobin,
platelets, spleen volume and liver volume, demonstrating progressive and clinically meaningful responses in
multiple organ systems. At three years, 100 percent of patients met at least 3 of the 4 therapeutic goals
developed for hematologic and organ volume parameters.
The three-year data also included analyses that suggest eliglustat tartrate positively impacts indicators of
bone disease through three years of follow up. These indicators include bone mineral density in the lumbar
spine, as measured by dual energy x-ray absorptiometry (DXA), and dark marrow signal in the femur, as
visualized by magnetic resonance imaging (MRI). Dark marrow reflects the infiltration of lipid-laden Gaucher
cells into bone marrow. Specifically:
- In the 18 patients at baseline with dark marrow in the femur visible by MRI, five improved by one year,
seven by two years and 10 by three years, with the other eight patients remaining stable.
- In the 15 patients with results available at all time points, bone mineral density in the lumbar spine showed
clinically and statistically significant improvements after one year of treatment (T score = +0.4) which further
improved after 2 years (T score = +0.6) and were sustained after three years of treatment.
Ravi S. Kamath, M.D., Ph.D., Staff Radiologist at Massachusetts General Hospital and Instructor in
Radiology at Harvard Medical School, who is the central radiology reviewer for the phase 2 study, said,
"These data suggest that eliglustat tartrate may have a meaningful clinical impact on bone disease in Gaucher
disease type 1 patients."
The most common adverse events (AEs) reported in greater than 2 patients through three years included
viral infections (six patients), urinary tract infections and upper respiratory infections (4 patients each),
headache, increased blood pressure, diarrhea and abdominal pain (three patients each). Eight drug-related
AEs, including one serious event, were reported in six patients. Most AEs overall and all drug-related AEs
were considered mild. The largest number of AEs was reported during the first 3 months of treatment.
"For thirty years, Genzyme has pioneered treatments for patients with lysosomal storage disorders, including
the very first enzyme replacement therapy for Gaucher disease," said Genzyme's President, Personalized
Genetic Health, John P. Butler. "Our momentum continues through the phase 3 trials - the largest ever
conducted for Gaucher - as we build upon our foundation and commitment to Gaucher and look to extend
the therapeutic options available to patients and physicians."
Eliglustat tartrate, a capsule taken orally, is being developed to provide a convenient treatment alternative for
adult patients with Gaucher disease type 1, and to offer a broader range of treatment options for patients
and physicians to achieve individual therapeutic goals. Genzyme is currently enrolling patients in three global,
multi-center, phase 3 trials of eliglustat tartrate. This is the largest clinical program ever focused on Gaucher
disease, with over 50 sites in more than 25 countries currently participating. Genzyme's Gaucher disease
portfolio also offers Cerezyme® (imiglucerase for injection), the standard of care for patients with Gaucher
disease type 1, which is administered through intravenous infusions.
About Gaucher disease
Gaucher disease is an inherited condition affecting fewer than 10,000 people worldwide. People with
Gaucher disease do not have enough of an enzyme, acid ß-glucosidase (glucocerebrosidase) that breaks
down a certain type of fat molecule. As a result, lipid engorged cells (called Gaucher cells) amass in different
parts of the body, primarily the spleen, liver and bone marrow. Accumulation of Gaucher cells may cause
spleen and liver enlargement, anemia, excessive bleeding and bruising, bone disease and a number of other
signs and symptoms. The most common form of Gaucher disease, type 1, does not typically affect the
nervous system and brain.
About eliglustat tartrate
Eliglustat tartrate, a novel glucosylceramide analog given orally, is designed to partially inhibit the enzyme
glucosylceramide synthase, which results in reduced production of glucosylceramide. Glucosylceramide is
the substance that builds up in the cells and tissues of people with Gaucher disease. In preclinical studies, the
molecule, developed with James A. Shayman, M.D. from the University of Michigan, has shown high
potency and specificity. Based on its mechanism of action, which is independent of genotype, eliglustat
tartrate may be a potential therapy for patients with Gaucher disease type 1. Initiation of the phase 2 and 3
studies of eliglustat tartrate in Gaucher disease followed completion of an extensive pre-clinical research
effort and a phase 1 program. Over 300 subjects have now been treated in nine separate studies.
The data from the phase 2 trials with eliglustat tartrate were previously published in the journal Blood and
the results can be found at the below references:
- Phase 2 data at the 1 year time point: Lukina et al. Blood, Aug 2010; Vol. 116: 893 - 899
- Phase 2 data at the 2 year time point: Lukina et al. Blood, Nov 2010; Vol 116: 4095 - 4098
Cerezyme important safety information
Approximately 15 percent of patients have developed IgG antibodies, and these patients have a higher risk
of hypersensitivity reaction. Therefore periodic monitoring is suggested; caution should be exercised in
patients with antibodies or prior symptoms of hypersensitivity. Symptoms suggestive of hypersensitivity
occurred in 6.6 percent of patients, and include anaphylactoid reaction, pruritus, flushing, urticaria,
angioedema, chest discomfort, dyspnea, coughing, cyanosis and hypotension. Reactions related to
Cerezyme administration have been reported in less than 15 percent of patients. Each of the following events
occurred in less than 2 percent of the total patient population. Reported adverse events include nausea,
vomiting, abdominal pain, diarrhea, rash, fatigue, headache, fever, dizziness, chills, backache, and
tachycardia. Adverse events associated with the route of administration include discomfort, pruritus, burning,
swelling or sterile abscess at the site of venipuncture.
Source:
Genzyme Corporation
February 24, 2011 - Spinal Fluid Proteins Distinguish Lyme Disease From Chronic Fatigue Syndrome –
Patients who suffer from Neurologic Post Treatment Lyme disease (nPTLS) and those with the Chronic
Fatigue Syndrome report similar symptoms. However unique proteins discovered in spinal fluid can
distinguish those two groups from one another and also from people in normal health, according to new
research conducted by a team led by Steven E. Schutzer, MD, of the University of Medicine and Dentistry
of New Jersey New Jersey Medical School, and Richard D. Smith, Ph.D., of Pacific Northwest National
Laboratory. This finding, published in the journal PLoS ONE (February 23, 2011), also suggests that both
conditions involve the central nervous system and that protein abnormalities in the central nervous system are
causes and/or effects of both conditions.
The investigators analyzed spinal fluid from three groups of people. One group consisted of 43 patients who
fulfilled the clinical criteria for Chronic Fatigue Syndrome (CFS). The second group consisted of 25 patients
who had been diagnosed with, and treated for, Lyme disease but did not completely recover. The third
group consisted of 11 healthy control subjects. "Spinal fluid is like a liquid window to the brain," says Dr.
Schutzer. By studying the spinal fluid, the research team hoped to find abnormalities that could be used as
markers of each condition and could lead to improvements in diagnosis and treatment.
Taking advantage of previously unavailable methods for detailed analysis of spinal fluid, the investigators
analyzed the fluid by means of high powered mass spectrometry and special protein separation techniques.
They found that each group had more than 2,500 detectable proteins. The research team discovered that
there were 1) 738 proteins that were identified only in CFS but not in either healthy normal controls or
patients with nPTLS; 2) 692 proteins found only in the nPTLS patients. Previously there had been no
available candidate biomarkers to distinguish between the two syndromes, nor even strong evidence that the
central nervous system is involved in those conditions.
This research represents the most comprehensive analysis of the complete spinal fluid proteome (collection
of proteins) to date for both Chronic Fatigue Syndrome and Neurologic Post Treatment Lyme disease
(nPTLS). Prior to this study, many scientists believed that CFS was an umbrella category that included
nPTLS. However these results call those previous suppositions into question,
According to Dr. Schutzer, spinal fluid proteins can likely be used as a marker of disease, and this study
provides a starting point for research in that area. "One next step will be to find the best biomarkers that will
give conclusive diagnostic results," he says. "In addition, if a protein pathway is found to influence either
disease, scientists could then develop treatments to target that particular pathway."
"Newer techniques that are being developed by the team will allow researchers to dig even deeper and get
more information for these and other neurologic diseases, says Dr. Smith. "These exciting findings are the tip
of our research iceberg"
Other authors included Thomas E. Angel, Tao Liu, Athena A. Schepmoes, Therese R. Clauss, Joshua N.
Adkins and David G. Camp II of PNNL; Bart K. Holland of UMDNJ-New Jersey Medical School; Jonas
Bergquist of Uppsala University in Sweden; P.K. Coyle of SUNY-Stony Brook; Brian A. Fallon of
Columbia University; Benjamin H. Natelson of UMDNJ, Beth Israel Medical Center and Albert Einstein
School of Medicine.
Funding sources included the National Institutes of Health, through NIAID, NIDA, NINDS, the National
Center for Research Resources, the Swedish Research Council, Uppsala Berzelii Technology Center for
Neurodiagnostics, SciLifeLab-Uppsala, Environmental Molecular Sciences Laboratory, Pacific Northwest
National Laboratory. Time for Lyme, Lyme Disease Association, and the Tami Fund.
Journal citation: Schutzer SE, Angel TE, Liu T, Schepmoes AA, Clauss TR, et al. (2011) Distinct
Cerebrospinal Fluid Proteomes Differentiate Post-Treatment Lyme Disease from Chronic Fatigue
Syndrome. PLoS ONE 6(2): e17287. doi:10.1371/journal.pone.0017287
Source: University of Medicine and Dentistry of New Jersey (UMDNJ)
February 25, 2011 - Seeking Out Sentinel Lymph Nodes Of Breast Cancer Patients Using Microbubbles
To Light The Way –
Researchers at the University of California, San Diego are developing nonsurgical methods for identifying
critical lymph nodes to help doctors determine courses of treatment for breast cancer patients. The "sentinel
lymph node" is routinely biopsied or removed and dissected to determine the likelihood that the cancer has
spread beyond the breast. Dr. Andrew Goodwin, a post doctoral fellow in the Department of
Nanoengineering in the UC San Diego Jacobs School of Engineering recently received a Breast Cancer
Postdoctoral Fellowship Award from the U.S. Department of Defense to use novel microbubbles to mark
and interrogate the sentinel lymph node by means of a simple ultrasound scan.
"Since analysis of tumor stage is important for all breast cancer patients, this work would be expected to
help many patients," explained Goodwin.
Cancer cells can detach from a primary tumor and enter the bloodstream by way of the lymph nodes. To
determine if the cancer is spreading to other parts of the body, surgeons will biopsy or remove the lymph
nodes to look for invading cells. Finding cancer cells in the lymph nodes often changes the course of
treatment in an effort to kill any cancer cells that have already spread beyond the breast. Removing just the
first, or sentinel, lymph node for analysis helps to reduce the likelihood of developing lymphedema, a painful,
long-term swelling at the area of dissection.
The benefits of sentinel lymph node dissection for breast cancer patients were underscored by research
findings recently published in The Journal of the American Medical Association.
However, identifying the correct lymph node to remove is not straightforward. Current methods require
injection of radioactive colloids, which tend to blur at the injection site, or blue dye, which leaches into
multiple nodes and can only be observed after opening up the patient. These "black box" methods provide
little information about the structure of the lymph nodes at the tumor site, and both require the patient to be
prepared for a surgery that may be unnecessary if the contrast administration is unsuccessful.
Ultrasound and Microbubbles
"I'm trying to develop a better way to mark the sentinel lymph node," says Goodwin. His approach involves
using ultrasound - high-frequency sound waves used in medical imaging applications such as prenatal
sonograms - and gas-filled microbubbles with fluorescent outer shells. These microbubbles capable of
loading large amounts of dye are described in a recent article in the journal Soft Matter by Goodwin and
coworkers.
If Goodwin's vision translates to the clinic, a physician would inject the fluorescent microbubbles into the
tumor and then use ultrasound to visualize the bubbles as they drain away from the tumor and into the lymph
nodes under the arm. Once the lymph nodes have been imaged and the sentinel lymph node identified, the
radiologist will turn up the power of the ultrasound beam - but just in the area surrounding the sentinel lymph
node. This will burst the microbubbles and release non-toxic fluorescent polymer that is designed to stick
specifically in the lymph nodes for extended periods, allowing both the doctor and patient to adequately
prepare for the lymph node dissection surgery.
For now, critical next steps include testing how the outer shell of the microbubbles interact with the lymph
node lining, as well as tests in animal models.
Goodwin's UC San Diego collaborators include his mentor Sadik Esener, Director of the NanoTumor
Center for Cancer Nanotechnology, and Professor of NanoEngineering and of Electrical and Computer
Engineering at the Jacobs School of Engineering, and Radiology Professor Robert Mattrey, M.D. from the
UCSD Moores Cancer Center. Last year, Dr. Goodwin also received a Pathway to Independence (K99)
Award in Cancer Nanotechnology from the National Institute of Health on his work related to designing
microbubbles for site-specific ultrasound imaging of malignant blood clots.
Source:
Daniel Kane
University of California - San Diego
February 25, 2011 - Researchers Identify New, More Effective Tool In Diagnosing Breast Cancer And
Melanoma In Sentinel Lymph Nodes –
Researchers say a new kind of tracing agent is more accurate than current methods in helping identify tumor-
draining sentinel lymph nodes in breast cancer and melanoma patients. That's the finding in a new study that
appears in the online version of the Annals of Surgical Oncology.
"This is an important finding for both physicians, and patients," says Stanley Leong, M.D., M.S., F.A.C.S.,
Chief of Cutaneous Surgery at California Pacific Medical Center and the lead author of the study. "We are
always trying to find better ways of identifying which lymph nodes are cancerous, this new approach does
just that with great accuracy, almost 90 percent of the time, and without any apparent safety issues."
Dr. Leong and his team used Lymphoseek, a radioactive tracing agent developed by Neoprobe, to see how
effective it was in mapping the spread of two solid tumor cancers breast and melanoma to surrounding or
sentinel lymph nodes, the first nodes to receive lymph drainage from a tumor.
Lymphoseek was injected into 78 patients (47 of them melanoma patients, 31 breast cancer patients) 55 of
whom then underwent imaging scans to map its movement through the lymph system. In more than 94
percent of these patients, Lymphoseek was able to identify a tumor draining lymph node before surgery.
In this Phase 2 trial Lymphoseek showed that it did not cause any reaction at the site of injection, reached
the targeted sentinel nodes faster than existing methods and was less likely to spread beyond the targeted
nodes to other more distant nodes.
Previous studies have shown that solid tumors, such as breast cancer and melanoma, use the lymphatic
system to spread to other parts of the body, including some regional sentinel nodes. Identifying how far
those tumors have spread and what nodes are affected can help identify how extensive the treatment needs
to be and can potentially limit the number of nodes that need to be removed.
"Our goal as surgeons is to remove only those nodes we need to and to avoid removing those not showing
any signs of cancer," says Dr. Leong. "Lymphoseek seems to be more accurate at giving us this information
than other mapping methods and that can hopefully help patients avoid unnecessary surgery."
Existing methods for mapping the spread of these tumors are relatively accurate but are all "off label" in that
they have not been approved by the Food and Drug Administration (FDA) for that use. Neoprobe is hoping
that this trial will enable it to move forward in applying for FDA approval for Lymphoseek as the first tracing
agent specifically radio-labeled for lymph node detection.
Source: California Pacific Medical Center
February 26, 2011 - Validation Of A Gene Expression To Distinguish Metastasizing From Non-
Metastasizing Head And Neck Cancers –
The validation of a test, based on gene expression and predicting the tumours that will metastasize in lymph
nodes of head & neck cancers, was presented today at the 3rd International Conference on innovative
approaches in Head and Neck Oncology (ICHNO), in Barcelona.
Dr Robert Takes, from the Radboud University Nijmegen Medical Centre, the Netherlands, reported results
of a study involving 222 cases of oral or oropharyngeal cancer. The study was jointly led by scientists from
Nijmegen and the University Medical Center Utrecht, and involved all eight head and neck oncological
centres of the Netherlands.
"Today, it is impossible with current diagnostic tools to detect small lymph node metastasis in patients with
head and neck squamous cell carcinoma and therefore it is common practice to operate on the neck even if
no metastases have been detected," said Dr Takes. "The majority of these operations is unnecessary
because, in most cases, no metastases are present."
If the chance of metastasis could be predicted more accurately, the number of operations could be reduced.
"In our study, determining gene expression changes in the primary tumour improved the distinction between
tumours that do metastasize from those that don't," continued Dr Takes.
With an array containing a set of 825 relevant genes, identified in a prior study and suitable for clinical
application, distinction between metastasizing and non-metastasizing tumours was possible. The test
correctly predicted the absence of metastasis in 89% of the cases.
"This is the first biological test that was able to obtain a high level of accuracy and has been validated in
multiple centres on a large cohort of patients," said Dr Takes.
"The possible reduction of unnecessary neck treatments in case of a negative test may result in decreased
morbidity without deterioration of oncological outcomes. Also, in the remaining cases that still develop
metastasis in the neck, salvage treatment is still possible," added Dr Takes.
This signature is an additional method to already existing means to assess the neck, like imaging techniques
and sentinel node procedures. "One important message arising from the study is that the combination of
biological (gene signature) and clinical factors did better than either alone," commented Prof Adrian Begg
from the Netherlands Cancer Institute (NKI). "It thus appears that this signature is a useful addition which
can help the decision on treatment policy."
"Treatment is usually mainly selected based on the anatomical extent of the primary tumour and its
metastasis. Additional biological information on the behaviour of each individual tumour could result in a
more tailored treatment resulting in better survival," said Dr Takes.
"Takes and colleagues have carried out an important and essential step in all studies on gene signatures,"
concluded Prof Begg, "namely to move on from the initial finding of potential prognostic or predictive
significance to validation in an independent clinical series."
"We look forward to further validation and refinement of this approach which opens promising
developments. In such studies it would still be useful to look at genome-wide expression, which would
provide the opportunity to not only validate the present signature but also to look for even better ones."
Source:
Cecile Hardon-Villard
European Society for Medical Oncology