Page updated 6/3/11
 |
| |
 |
| |
 |
Lymphland International Lymphedema Online
May 7, 2011
Vojnosanit Pregl. 2011 Mar;68(3):270-3.
[Congenital intestinal lymphangiectasia].
[Article in Serbian]
Popović DD, Spuran M, Alempijević T, Krstić M, Djuranović S, Kovacević N, Damnjanović S, Micev M.
Source
Klinicki centar Srbije, Sluzba za patohistologiju, Beograd, Srbija. dr.popovic@sezampro.rs
Abstract
BACKGROUND:
Congenital intestinal lymphangiectasia is a disease which leads to protein losing enteropathy. Tortuous,
dilated lymphatic vessels in the intestinal wall and mesenterium are typical features of the disease. Clinical
manifestations include malabsorption, diarrhea, steatorrhea, edema and effusions. Specific diet and
medication are required for disease control.
CASE REPORT:
A 19-year old male patient was hospitalized due to diarrhea, abdominal swelling, weariness and fatigue.
Physical examination revealed growth impairment, ascites, and lymphedema of the right hand and forearm.
Laboratory assessment indicated iron deficiency anaemia, lymphopenia, malabsorption, inflammatory
syndrome, and urinary infection. Enteroscopy and video capsule endoscopy demonstrated dilated lymphatic
vessels in the small intestine. The diagnosis was confirmed by intestinal biopsy. The patient was put on high-
protein diet containing medium-chain fatty acids, somatotropin and supportive therapy.
CONCLUSION:
Congenital intestinal lymphangiectasia is a rare disease, usually diagnosed in childhood. Early recognition of
the disease and adequate treatment can prevent development of various complications.
PMID: 21526555 [PubMed - in process
Clin Radiol. 2011 Apr 23. [Epub ahead of print]
Regional diagnosis of lymphoedema and selection of sites for lymphaticovenular anastomosis using
elastography.
Mihara M, Hayashi Y, Murai N, Moriguchi H, Iida T, Hara H, Todokoro T, Narushima M, Uchida G,
Koshima I.
Source
Department of Plastic Surgery and Reconstructive Surgery, The University of Tokyo, Tokyo.
Abstract
AIM:
To evaluate the use of ultrasound elastography as a basis for determining the most appropriate sites for
lymphaticovenular anastomosis (LVA) for treatment of lymphoedema.
MATERIALS AND METHODS:
Preoperative elastography and LVA were performed in 11 patients (11 legs) with leg lymphoedema,
including two cases of primary oedema and nine of secondary oedema.
RESULTS:
The mean number of LVAs applied per leg was 4.4 (range 3-7). The mean reduction in the leg
circumference was 91.7%, and 10 of the 11 cases (90.0%) were improved. Hardness was reduced from a
mean of 1.6 before surgery to 0.9 after surgery, and improvement was also noted in 10 cases (90.9%). The
severity of oedema was determined in five regions in each leg, and was classified as elastography stage (ES)
0 in 11 regions, ES1 in 23, ES2 in 15, and ES3 in six.
CONCLUSIONS:
These results demonstrate the value of ultrasound elastography for the diagnosis of early-stage
lymphoedema and determination of LVA sites. This is the first report of diagnosis of lymphoedema using
elastography and the findings suggest that this procedure followed by LVA could be used as a new
therapeutic method for early-stage lymphoedema.
Copyright © 2011 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.
PMID: 21524415 [PubMed - as supplied by publisher]
Arch Phys Med Rehabil. 2011 May;92(5):756-764.e1.
Assessment of lymphatic contractile function after manual lymphatic drainage using near-infrared
fluorescence imaging.
Tan IC, Maus EA, Rasmussen JC, Marshall MV, Adams KE, Fife CE, Smith LA, Chan W, Sevick-
Muraca EM.
Source
Center for Molecular Imaging, The Brown Foundation Institute of Molecular Medicine, The University of
Texas Health Science Center, Houston, TX; Formerly, Department of Radiology, Baylor College of
Medicine, Houston, TX.
Abstract
Tan I-C, Maus EA, Rasmussen LC, Marshall MV, Adams KE, Fife CE, Smith LA, Chan W, Sevick-
Muraca EM. Assessment of lymphatic contractile function after manual lymphatic drainage using near-
infrared fluorescence imaging.
OBJECTIVE:
To investigate the feasibility of assessing the efficacy of manual lymphatic drainage (MLD), a method for
lymphedema (LE) management, by using near-infrared (NIR) fluorescence imaging.
DESIGN:
Exploratory pilot study.
SETTING:
Primary care unit.
PARTICIPANTS:
Subjects (N=10; age, 18-68y) with a diagnosis of grade I or II LE and 12 healthy control subjects (age, 22-
59y).
INTERVENTION:
Indocyanine green (25 μg in 0.1 mL each) was injected intradermally in bilateral arms or legs of subjects.
Diffused excitation light illuminated the limbs, and NIR fluorescence images were collected by using custom-
built imaging systems. Subjects received MLD therapy, and imaging was performed pre- and posttherapy.
MAIN OUTCOME MEASURES:
Apparent lymph velocities and periods between lymphatic propulsion events were computed from
fluorescence images. Data collected pre- and post-MLD were compared and evaluated for differences.
RESULTS:
By comparing pre-MLD lymphatic contractile function against post-MLD lymphatic function, results showed
that average apparent lymph velocity increased in both the symptomatic (+23%) and asymptomatic (+25%)
limbs of subjects with LE and control limbs (+28%) of healthy subjects. The average lymphatic propulsion
period decreased in symptomatic (-9%) and asymptomatic (-20%) limbs of subjects with LE, as well as in
control limbs (-23%).
CONCLUSIONS:
We showed that NIR fluorescence imaging could be used to quantify immediate improvement of lymphatic
contractile function after MLD.
Copyright © 2011 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights
reserved.
PMID: 21530723 [PubMed - in process]
May 10, 2011
3,7-bis(dimethylamino)-phenothiazin-5-ium chloride.
Authors
Chopra A.
Source
Molecular Imaging and Contrast Agent Database (MICAD) [Internet]. Bethesda (MD): National Center for
Biotechnology Information (US); 2004-2011.
2011 Apr 05 [updated 2011 Apr 29].
Excerpt
A sentinel lymph node (SLN)is the first lymph node showing presence of metastasized cancer cells from a
tumor. An SLN biopsy (SLNB) is the method of choice to stage breast cancer (i.e., to describe the stage of
cancer progress using numbers I to IV, going from low to highest progression) in patients exhibiting clinically
negative (i.e., without metastases) axillary lymph nodes (1, 2). Once detected and confirmed, the metastatic
spread of the cancer from the primary tumor to the axillary lymph nodes through the lymphatic system is then
tracked with either a radiolabeled sulfur colloid and/or a blue dye (isosulfan blue or methylene blue; neither
of these dyes are approved by the United States Food and Drug Administration (FDA) for this application)
(2). After visual confirmation, the SLN is surgically resected, and the definitive presence of cancer is
established with histological methods. Although the SLNB procedure is minimally invasive, it has a 5%–10%
false negative rate of detecting cancer and can possibly lead to lymphedema, seroma formation (collection of
fluid under the skin), injury to local sensory nerves, and a reduction in the patient's range of motion (1, 2). In
some cases, ultrasonography (US), which is the detection of high frequency sound waves, is used to identify
a SLN, and a biopsy is obtained with a fine-needle aspiration biopsy (FNAB). The biopsy sample is then
subjected to molecular analysis using the real-time reverse transcription-polymerase chain reaction to detect
cancer in the tissue from the breast. A limitation of using US to identify a SLN is that it can only determine
the size and shape of the lymph node but cannot specifically distinguish between a cancerous and a non-
cancerous lymph node; this limitation reduces the sensitivity of the FNAB procedure to detect a malignancy
(3). Photoacoustic imaging (PAI) is a noninvasive method that does not involve the use of ionizing radiation
for the detection of cancer. This technique, which uses a combination of the optical and US imaging
modalities to detect malignant lesions, angiogenesis, etc (4), has been described in detail elsewhere (5). In
brief, application of a pulse of light to biological tissue results in the generation of ultrasonic waves
(photoacoustic waves) due to the thermoelastic expansion and contraction of the tissue (i.e., a fraction of the
light is converted into heat within the tissue). Subsequently, the photoacoustic waves are captured with a
suitable device (transducer) that captures the US waves and converts them into an image. If used by itself,
optical imaging has a limited imaging depth and spatial resolution because light is scattered by the tissue. As
a result, images generated with US alone have a low contrast and are speckled (5). The main advantage of
using PAI is that the depth and resolution of an image can be improved by controlling the detection
frequency of the transducer, and the quality of the images can be further enhanced by using intrinsic contrast
agents (e.g., melanin and hemoglobin) or exogenous contrast agents (e.g., an organic dye such as methylene
blue, nanoparticles, etc.) (5). Methylene blue is an aromatic compound that has many applications in biology
and medicine. In the laboratory, methylene blue is often used to stain blood cells for histological
investigations, to detect nucleic acids on blots, and to determine the viability of yeast cells. Although
methylene blue is not approved for clinical use by the FDA, it is available commercially in the United States
for off label use as an intravenous injection to treat methemoglobinemia. Methylene blue is also under
investigation in clinical trials to treat osteoarthritis, to detect invasive aspergillosis, and to map and localize
SLN in breast and thyroid cancer patients. In several European countries, a procedure using methylene blue
has been approved to reduce the pathogen load (e.g., viruses such as HIV and hepatitis B and C) in
individual units of human plasma to be used for transfusion purposes (6). It has been shown that methylene
blue radiolabeled with astatine-211 is suitable for the diagnosis and selective treatment of melanoma in mice
(7). Investigators have also shown that methylene blue encapsulated in nanoparticles can be used for in vivo
imaging and photodynamic therapy in mice (exposure of methylene blue nanoparticles to high-energy light
pulses results in the production of nascent oxygen that damages the nucleic acids in the cells) (8). Recently,
in an effort to develop an alternative method to SLNB and FNAB for the detection of SLNs in breast
cancer patients, methylene blue has been successfully used as a contrast agent to visualize SLN in rats with
PAI (1, 2).
Sections
Background
Synthesis
In Vitro Studies: Testing in Cells and Tissues
Animal Studies
Human Studies
Supplemental Information
NIH Support
References
PMID: 21542554 [PubMed)}
May 11, 2011
Ann Plast Surg. 2011 May 2. [Epub ahead of print]
Vascularized Lymph Node Transfer Based on the Hilar Perforators Improves the Outcome in Upper Limb
Lymphedema.
Gharb BB, Rampazzo A, di Spilimbergo SS, Xu ES, Chung KP, Chen HC.
Source
From the *Plastic Surgery Department, China Medical University Hospital, Taichung, Taiwan; and
†Department of Public Health, Institute of Health Care Organization Administration, College of Public
Health, National Taiwan University, Taipei, Taiwan.
Abstract
BACKGROUND:
Maintenance of the blood supply to the lymph nodes is necessary for survival and function. We report the
outcome of vascularized lymph node transfer with hilar perforators compared with the conventional
technique.
PATIENTS:
A total of 21 patients affected by early stage II upper limb lymphedema were included in this study. Of
them, 11 patients received a free groin flap containing lymph nodes and 10 patients received vascularized
inguinal lymph nodes with hilar perforators. Mean follow-up was 46 and 40 months, respectively.
Complications, secondary procedures, circumference of the limb, and subjective symptomatology were
registered. The differences were evaluated statistically.
RESULTS:
The limb circumferences decreased significantly in the new group. The number of secondary procedures was
significantly higher in the standard group. There were 2 cases of partial flap loss and donor site lymphorrhea
in the standard group. In both the groups, visual analog scale scores improved after the operation.
CONCLUSIONS:
Transfer of vascularized inguinal lymph nodes based on the hilar perforators improves the outcomes in the
treatment of early lymphedema of the upper extremity.
PMID: 21540737 [PubMed - as supplied by publisher]
Commun Agric Appl Biol Sci. 2011;76(1):189-92.
Assessment of skinfold thickness as a factor related to chronic progressive lymphoedema in Belgian draught
horses.
De Keyser K, Peeters LM, Buys N, Janssens S.
Source
Laboratory of Livestock Genetics, Department of Biosystems, K.U.Leuven, Kasteelpark Arenberg 30, bus
2456, 3001 Leuven, Belgium.
PMID: 21539228 [PubMed - in process]
Ann Surg Oncol. 2011 May 3. [Epub ahead of print]
Therapeutic Surgical Management of Palpable Melanoma Groin Metastases: Superficial or Combined
Superficial and Deep Groin Lymph Node Dissection.
van der Ploeg AP, van Akkooi AC, Schmitz PI, van Geel AN, de Wilt JH, Eggermont AM, Verhoef C.
Source
Department of Surgical Oncology, Erasmus University Medical Center - Daniel den Hoed Cancer Center,
Rotterdam, The Netherlands.
Abstract
BACKGROUND:
Management of patients with clinically detectable lymph node metastasis to the groin is by ilioinguinal or
combined superficial and deep groin dissection (CGD) according to most literature, but in practice
superficial groin dissection (SGD) only is still performed in some centers. The aim of this study is to evaluate
the experience in CGD versus SGD patients in our center.
METHODS:
Between 1991 and 2009, 121 therapeutic CGD and 48 SGD were performed in 169 melanoma patients
with palpable groin metastases at our institute. Median follow-up was 20 and, for survivors, 45 months.
RESULTS:
In this heterogeneous group of patients, overall (OS) and disease-free survival, local control rates, and
morbidity rates were not significantly different between CGD and SGD patients. However, CGD patients
had a trend towards more chronic lymphedema. Superficial lymph node ratio, the number of positive
superficial lymph nodes, and the presence of deep nodes were prognostic factors for survival. CGD patients
with involved deep lymph nodes (24.8%) had estimated 5-year OS of 12% compared with 40% with no
involved deep lymph nodes (p = 0.001). Preoperative computed tomography (CT) scan had high negative
predictive value of 91% for detection of pelvic nodal involvement.
CONCLUSIONS:
This study demonstrated that survival and local control do not differ for patients with palpable groin
metastases treated by CGD or SGD. Patients without pathological iliac nodes on CT might safely undergo
SGD, while CGD might be reserved for patients with multiple positive nodes on SGD and/or positive deep
nodes on CT scan.
PMID: 21537867 [PubMed - as supplied by publisher]
Br J Nurs. 2011 Apr 14-27;20(7):418, 420, 422.
Use of compression hosiery in chronic oedema and lymphoedema.
Lay-Flurrie K.
Source
St Albans City Hospital.
Abstract
The management of chronic oedema is a continuing partnership between patient and practitioner and
accurate diagnosis and treatment planning are essential to control the condition in order to prevent
complications and optimise the patient's quality of life. A paucity of funding, lack of knowledge and
confidence on the part of practitioners and widely varying access to services means that many patients face
barriers to gaining appropriate treatment. Nurses in many spheres will come across patients with some form
of chronic oedema. The following article describes the types and causes of chronic oedema and
lymphoedema and explores the use of compression hosiery as one facet in management of the condition.
Patient education and the role of the practitioner are also highlighted to develop awareness of the need for
adequate preparation of a patient to facilitate concordance and self-management of their condition.
PMID: 21537258 [PubMed - in process]
Plast Reconstr Surg. 2011 May;127(5):1987-92.
Lambda-shaped anastomosis with intravascular stenting method for safe and effective lymphaticovenular
anastomosis.
Yamamoto T, Narushima M, Kikuchi K, Yoshimatsu H, Todokoro T, Mihara M, Koshima I.
Source
Tokyo, Japan From the Department of Plastic and Reconstructive Surgery, Graduate School of Medicine,
University of Tokyo.
Abstract
BACKGROUND:
: Lymphaticovenular anastomosis has become an increasingly common treatment for lymphedema.
Supermicrosurgical techniques are essential for the successful performance of lymphaticovenular
anastomosis. A positive correlation between the number of lymphaticovenular anastomoses performed and
therapeutic efficacy has been reported, and in performing these anastomoses, the establishment of as many
bypasses as possible is important.
METHODS:
: Forty limbs of 20 patients with lower extremity lymphedema who underwent lymphaticovenular
anastomosis in our department were assessed. All cases were performed under local anesthesia using two to
four surgical microscopes. A new method of anastomosis, lambda-shaped anastomosis assisted by
intravascular stenting, was chosen in required cases.
RESULTS:
: Lymphaticovenular anastomoses resulted in 186 anastomoses on 20 patients with lower extremity
lymphedema; the average number of anastomoses per case was 9.3 (range, five to 18). The number of
surgical microscopes used ranged from two to four (average, 3.3), and the duration of the operation ranged
from 3 to 5 hours (average, 4.1). In the cases of lambda-shaped anastomosis (n = 11), the number of
anastomoses was significantly greater than in the cases without lambda-shaped anastomosis (n = 9; 10.2 ±
2.3 versus 8.2 ± 1.4; p < 0.05).
CONCLUSIONS:
: Lambda-shaped anastomosis assisted by intravascular stenting is a safe and relatively easy method that can
be performed by surgeons with less than 1 year of experience in microsurgery. This in turn allows efficient
lymphaticovenular anastomoses to be performed simultaneously by a team of surgeons, resulting in an
increased number of bypasses.
PMID: 21532425 [PubMed - in process]
Plast Reconstr Surg. 2011 May;127(5):1979-86.
Characteristic indocyanine green lymphography findings in lower extremity lymphedema: the generation of a
novel lymphedema severity staging system using dermal backflow patterns.
Yamamoto T, Narushima M, Doi K, Oshima A, Ogata F, Mihara M, Koshima I, Mundinger GS.
Source
Tokyo, Japan; and Baltimore, Md. From the Department of Plastic and Reconstructive Surgery, Graduate
School of Medicine, University of Tokyo, and Division of Plastic, Reconstructive, and Maxillofacial Surgery,
The Johns Hopkins Hospital.
Abstract
BACKGROUND:
: Indocyanine green lymphography has been a highly useful modality in the clinical examination and surgical
management of patients with lymphedema. No formal classification system of indocyanine green imaging
findings according to the severity of lymphedema exists, however. The purpose of this study was to
describe, analyze, and classify characteristic indocyanine green lymphography findings to uniformly guide
surgical management of lymphedema using this modality.
METHODS:
: Forty-five patients (78 limbs) with lower extremity lymphedema underwent indocyanine green
lymphography. All lymphography images were recorded in photographs and videos. Images were reviewed
and analyzed to classify characteristic findings according to clinical severity as determined by Campisi clinical
lymphedema staging.
RESULTS:
: Lymphography findings were classifiable into two patterns. Mild cases of lymphedema were characterized
by a linear lymphatic channel pattern (linear pattern). In more severe cases, lymphatic channels
demonstrated retrograde lymphatic flow (dermal backflow pattern) and diminution or absence of linear
channel patterning. Three dermal backflow patterns, splash, stardust, and diffuse, were identified and
correlated with the progression of lymphedema severity. These findings supported the generation of a novel
anatomical lymphedema severity staging system, the dermal backflow staging system.
CONCLUSIONS:
: Indocyanine green lymphography is a safe, minimally invasive, and useful tool for the surgical evaluation of
extremity lymphedema. Characteristic indocyanine green lymphography patterns are consistent and correlate
with clinical severity. The dermal backflow staging system can facilitate patient stratification, discussion
between referring parties, and surgical planning.
PMID: 21532424 [PubMed - in process]
Plast Reconstr Surg. 2011 May;127(5):1804-11.
Microsurgical lymphaticovenous implantation targeting dermal lymphatic backflow using indocyanine green
fluorescence lymphography in the treatment of postmastectomy lymphedema.
Furukawa H, Osawa M, Saito A, Hayashi T, Funayama E, Oyama A, Sekido M, Yamamoto Y.
Source
Sapporo, Japan From the Department of Plastic and Reconstructive Surgery, Graduate School of Medicine,
University of Hokkaido at Sapporo.
Abstract
BACKGROUND:
: Microsurgical lymphaticovenous implantation in lymphedema is done to create a lymphaticovenous shunt by
an implantation of collecting lymphatics into the small vein, as reported previously. The authors have recently
introduced ultrasonograpy and indocyanine green fluorescence lymphography into this procedure.
METHODS:
: Nine cases of postmastectomy lymphedema had received preoperative venous marking using
ultrasonography and lymphatic mapping using indocyanine green fluorescence lymphography. The concept
of modification is to pick up the most effective point for microsurgical lymphaticovenous implantation that
involves both subcutaneous veins and the dermal backflow of excess lymphatics. Objective improvement
was analyzed by the percent reduction of edema circumference at two points of the affected forearm.
RESULTS:
: Preoperative lymphography showed a spotty image for dermal backflow in all nine extremities, a linear
image on the dorsal hand in six extremities, and a linear image on the forearm in three extremities. With an
average follow-up of 17 months, three patients had excellent results with the reduction of edema
circumference more than 50 percent for both the distal and proximal sites of the treated forearm. Four
patients had good results with the reduction of edema circumference more than 50 percent at the distal or
proximal sites, two patients had fair results, and no patients had poor results. The average number of
modified microsurgical lymphaticovenous implantations was 3.7 per case.
CONCLUSION:
: Modified microsurgical lymphaticovenous implantation is expected to provide favorable results with a
minimum number of these modified implantations, even though no linear lymph channel was detected by
preoperative indocyanine green fluorescence lymphography.
PMID: 21532410 [PubMed - in process]
Arch Phys Med Rehabil. 2011 May;92(5):756-764.e1
Assessment of lymphatic contractile function after manual lymphatic drainage using near-infrared
fluorescence imaging.
Tan IC, Maus EA, Rasmussen JC, Marshall MV, Adams KE, Fife CE, Smith LA, Chan W, Sevick-
Muraca EM.
Source
Center for Molecular Imaging, The Brown Foundation Institute of Molecular Medicine, The University of
Texas Health Science Center, Houston, TX; Formerly, Department of Radiology, Baylor College of
Medicine, Houston, TX
.
Abstract
Tan I-C, Maus EA, Rasmussen LC, Marshall MV, Adams KE, Fife CE, Smith LA, Chan W, Sevick-
Muraca EM. Assessment of lymphatic contractile function after manual lymphatic drainage using near-
infrared fluorescence imaging.
OBJECTIVE:
To investigate the feasibility of assessing the efficacy of manual lymphatic drainage (MLD), a method for
lymphedema (LE) management, by using near-infrared (NIR) fluorescence imaging.
DESIGN:
Exploratory pilot study.
SETTING:
Primary care unit.
PARTICIPANTS:
Subjects (N=10; age, 18-68y) with a diagnosis of grade I or II LE and 12 healthy control subjects (age, 22-
59y).
INTERVENTION:
Indocyanine green (25 μg in 0.1 mL each) was injected intradermally in bilateral arms or legs of subjects.
Diffused excitation light illuminated the limbs, and NIR fluorescence images were collected by using custom-
built imaging systems. Subjects received MLD therapy, and imaging was performed pre- and posttherapy.
MAIN OUTCOME MEASURES:
Apparent lymph velocities and periods between lymphatic propulsion events were computed from
fluorescence images. Data collected pre- and post-MLD were compared and evaluated for differences.
RESULTS:
By comparing pre-MLD lymphatic contractile function against post-MLD lymphatic function, results showed
that average apparent lymph velocity increased in both the symptomatic (+23%) and asymptomatic (+25%)
limbs of subjects with LE and control limbs (+28%) of healthy subjects. The average lymphatic propulsion
period decreased in symptomatic (-9%) and asymptomatic (-20%) limbs of subjects with LE, as well as in
control limbs (-23%).
CONCLUSIONS:
We showed that NIR fluorescence imaging could be used to quantify immediate improvement of lymphatic
contractile function after MLD.
Copyright © 2011 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights
reserved.
PMID: 21530723 [PubMed - in process]
MED NEWS FORMATTED DOCS (2) :
May 4, 2011
Lymphoseek(R) (Tilmanocept) Meets All Endpoints In Neo3-09 Phase 3 Study
Neoprobe Corporation (NYSE Amex: NEOP), a diversified developer of innovative oncology diagnostic
products, today announced top-line results from its Lymphoseek(R) (tilmanocept) NEO3-09 study. The
NEO3-09 study met all primary and secondary endpoints and highlighted the superior performance by
Lymphoseek compared to vital blue dye in intraoperative lymphatic mapping (ILM), a procedure in which
lymph nodes are identified for biopsy to assess for the presence of tumor. The NEO3-09 Phase 3 clinical
study, the Company's second successful Phase 3 study for Lymphoseek, enrolled over 150 subjects with
either breast cancer or melanoma within the intent-to-treat (ITT) population. Lymphoseek performed
equally well in both cancer types. As previously disclosed by the Company, the full NEO3-09 data set will
be presented at the 2011 Annual Meeting of the American Society of Clinical Oncology, June 3-7, in
Chicago.
"The results from NEO3-09 are important not only in that they demonstrate that Lymphoseek is safe and
well-tolerated but in many ways that it is a clinically superior lymphatic mapping agent to vital blue dye," said
Dr. Vernon K. Sondak, Chief of the Division of Cutaneous Oncology at the H. Lee Moffitt Cancer Center
and Research Institute. "Currently, vital blue dyes like isosulfan blue are the only FDA-approved agents for
ILM. These blue dyes are helpful, but have significant limitations. Lymphoseek provided clinically meaningful
advantages over the blue dyes and I believe it will be a useful agent in ILM."
The primary endpoint of this study was the comparison, or concordance rate, of Lymphoseek versus vital
blue dye in ILM, where vital blue dye was designated as the "Truth Standard" comparator. NEO3-09 study
subjects yielded over 200 lymph nodes stained with vital blue dye. Of the vital blue dye stained nodes,
Lymphoseek detected all of them, a concordance rate of 100%, which is highly statistically significant. This
concordance rate was consistent with the rate observed in the NEO3-05 Phase 3 study of approximately
98%, which also was highly statistically significant.
Using Lymphoseek as the Truth Standard, the reverse concordance rate for vital blue dye was
approximately 60%, a finding similar to the retrospective reverse concordance rate observed in the NEO3-
05 Phase 3 study of approximately 69%. These data demonstrate that in these studies vital blue dye
statistically was not equivalent to, and in fact was inferior to, Lymphoseek in this measure of lymph node
detection.
Use of the concordance data and reverse concordance data in a pre-specified, prospective test of
superiority showed that Lymphoseek's performance was statistically superior to vital blue dye in lymph node
detection.
Lymphoseek also demonstrated a superior ability to detect lymph nodes that contained cancer. In NEO3-
09, the ILM procedures found pathology-confirmed, cancer-positive lymph nodes at a rate consistent with
the general rate of nodal involvement typically observed in these cancer types. Of these pathology-
confirmed, cancer-positive nodes, Lymphoseek detected all of them, for a failed detection rate of 0%. In
contrast, vital blue missed over 25% of cancer-positive nodes. This prospective analysis confirmed the
lower failed detection rate for Lymphoseek observed retrospectively in the NEO3-05 Phase 3 study.
Lymphoseek's substantially lower failed detection rate means that it missed fewer lymph nodes containing
cancer, a key finding given that the objective of ILM is to determine if the cancer has spread to the lymph
nodes.
In both NEO3-09 and NEO3-05, Lymphoseek demonstrated no drug-related serious adverse events or
clinically significant adverse events, whereas vital blue dye showed several significant drug-related adverse
events. In over 500 subjects receiving Lymphoseek to date, no clinically significant drug-related adverse
events have been reported.
In a full regional lymph node dissection procedure, a patient with breast cancer or melanoma may have as
many as 20 to 30 lymph nodes removed in order to determine whether or not cancer has spread to other
parts of their body. This very invasive procedure frequently causes significant side effects. In the NEO3-05
and NEO3-09 studies combined, Lymphoseek detected an average of 2.4 lymph nodes per patient,
whereas vital blue dye detected a similar average of approximately 1.5 lymph nodes per patient. With this
relatively small difference in number of nodes removed, Lymphoseek exhibited superior performance in
detecting lymph nodes containing cancer, as evidenced by its lower failed detection rate noted above. The
average number of lymph nodes detected by Lymphoseek in a much less invasive manner is still far below
the number of lymph nodes removed in full regional node dissection procedures, thus potentially sparing the
patient the morbidity and side effects commonly associated with more complete regional nodal dissection
procedures.
"The NEO3-09 Phase 3 study met its endpoints and confirmed the previous findings of high concordance
and superiority demonstrated in the first Phase 3 study, NEO3-05," said Dr. Fred Cope, Neoprobe's
Senior Vice President, Pharmaceutical Research and Clinical Development. "Lymphoseek also showed
superiority in detecting lymph nodes that contained tumor. This is important because detecting lymph nodes
bearing tumor is the underlying reason for performing ILM procedures to enable lymph-node biopsy."
"In clinical studies, Lymphoseek has been shown to be a safe and effective tool for superior detection of
lymph nodes and offers an enhanced ability to accurately identify nodes with a high potential of tumor
metastases" stated Dr. Mark Pykett, Neoprobe's President and CEO. "This results in lower failed detection
rates than the current standard approach in intraoperative lymphatic mapping using vital blue dye. With these
encouraging data, our plans are on track to submit the Lymphoseek New Drug Application to the FDA in
the third quarter."
About Lymphoseek
Lymphoseek is a proprietary radioactive diagnostic tracing agent being developed for use in connection with
gamma detection devices in a surgical procedure known as Intraoperative Lymphatic Mapping. Two Phase
3 multi-center clinical trials (clinicaltrials.gov, trial registration numbers NCT00671918 and NCT01106040)
for Lymphoseek in patients with breast cancer or melanoma have concluded. A third Phase 3 clinical study
to evaluate the efficacy of Lymphoseek as a sentinel lymph node tracing agent in patients with head and neck
squamous cell carcinoma is currently ongoing (clinicaltrials.gov, trial registration number NCT00911326).
May 5, 2011
Survivors Of Childhood Cancer Are At Increased Risk For Ongoing Post-Therapy GI Complications
Patients who received therapy for cancer during childhood have an increased risk of developing
gastrointestinal (GI) complications later in life, according to a new study in Gastroenterology, the official
journal of the American Gastroenterological Association (AGA) Institute. Compared with their siblings,
cancer survivors had an increased risk of late-onset complications of the upper GI tract, lower GI tract and
liver.
"Survivors are at elevated risk for ongoing gastrointestinal complications after therapy," said Robert
Goldsby, MD, of the University of California, San Francisco Children's Hospital and lead author of the
study. "Because these gastrointestinal complications may impact quality of life, health-care providers should
be aware of potential gastrointestinal problems in this population as they evaluate acute symptoms and plan
ongoing follow-up care."
As more children diagnosed with cancer are surviving long-term, it is increasingly important to recognize the
long-term consequences of their cancer and its therapy. This analysis shows that survivors of childhood
cancer have a higher incidence of self-reported GI complaints compared with their siblings. Risks for
colostomy/ileostomy, cirrhosis or liver biopsy were highest. Older age at diagnosis, exposure to abdominal
radiation and certain chemotherapy treatments increase that risk. More than 40 percent of childhood cancer
survivors reported a late GI complication by 20 years after cancer therapy. The probability of experiencing a
late GI consequence was greater in survivors compared to siblings. The survivor's prior experience may
increase their sensitivity to GI-related symptoms, but cancer treatments may cause direct damage to the GI
organ system.
"The risks of late GI complications may change as therapy for childhood and adolescent cancer continues to
evolve and will require studies of more recently treated patients," added Dr. Goldsby. Although various
disease-specific combinations of chemotherapy, radiation and surgery have dramatically improved survival,
these treatment modalities have the potential to cause significant GI complications. For example, abdominal
radiation often results in several acute toxicities, including intestinal inflammation and abnormal movement of
the intestinal tract. Chemotherapy is associated with many acute GI toxicities, including nausea, vomiting,
diarrhea, constipation and increased susceptibility to GI infections. Intra-abdominal surgery and subsequent
GI complications are also contributors to GI toxicity of cancer therapy. Long-term GI consequences,
however, have not been extensively studied.
In this study, doctors evaluated the incidence of long-term GI outcomes and identified treatment-related risk
factors. The goals of this analysis were to describe the incidence of self-reported adverse GI conditions
occurring at least five years after diagnosis and to evaluate the effect of different treatment-associated factors
on the risk of developing these GI events.
Upper GI, lower GI and liver adverse outcomes were assessed in cases from participants in the Childhood
Cancer Survivor Study, a study of 14,358 survivors of childhood cancer (i.e., leukemias, brain tumors,
lymphomas, Wilms tumor, neuroblastoma, sarcomas and bone tumors) who were diagnosed between 1970
and 1986 at one of 26 collaborating institutions in the U.S. and Canada; data were compared with those
from randomly selected siblings. The median age at cancer diagnosis was 6.8 years, and the median age at
outcome assessment was 23.2 years for survivors and 26.6 years for siblings.
May 15, 2011
Cancer Nurs. 2011 May 9. [Epub ahead of print]
Voices From the Shadows: Living With Lymphedema.
Ridner SH, Bonner CM, Deng J, Sinclair VG.
Source
Author Affiliations: Vanderbilt University School of Nursing, Nashville, Tennessee.
Abstract
BACKGROUND:
Breast cancer survivors with lymphedema face a lifetime of stressful physical and emotional symptoms and
challenging self-care demands. An in-depth understanding of the perceptions and feelings surrounding life
with lymphedema is critical to developing effective supportive care approaches.
OBJECTIVE:
The objective of the study was to explore perceptions and feelings related to lymphedema in breast cancer
survivors.
METHOD:
The expressive writings of 39 individuals were evaluated for this descriptive qualitative study. Data were
analyzed using conventional content analysis.
RESULTS:
Qualitative analyses produced 4 major themes: (1) marginalization and minimization, (2) multiplying losses,
(3) yearning to return to normal, and (4) uplifting resources. Subthemes for each major theme were also
identified.
CONCLUSION:
The lymphedema experiences of breast cancer survivors reveal perceptions of marginalization from health
care providers who are not well informed about lymphedema management and minimizing its impact.
Multiple distressing losses confront these patients on a daily basis, including body image disturbances, loss of
functionality and control over time, permanent uncertainty, and adverse effects on relationships. The daily
challenges of lymphedema often result in cumulative frustration and resentment that contribute to failure to
perform self-care. Normalcy has been lost, never to return. These women find solace, encouragement, and
hope to meet the challenges of lymphedema through support from others and their spiritual beliefs.
IMPLICATIONS FOR PRACTICE:
Health care providers need greater awareness of the physical and psychosocial effects of lymphedema in
breast cancer survivors. Nurses have unique opportunities to serve as advocates for reducing perceived
marginalization and promoting effective self-care and other activities that promote psychological well-being
and reduce physical deterioration.
PMID: 21558848 [PubMed - as supplied by publisher]
Support Care Cancer. 2011 May 8. [Epub ahead of print]
Compression garments versus compression bandaging in decongestive lymphatic therapy for breast cancer-
related lymphedema: a randomized controlled trial.
King M, Deveaux A, White H, Rayson D.
Source
Occupational Therapy, Capital District Health Authority, Room 326, NS Rehabilitation Center, 1341
Summer Street, Halifax, NS, B3H 4KY, Canada, myrna.king@cdha.nshealth.ca.
Abstract
BACKGROUND:
Lymphedema as a result of curative surgery for breast cancer can lead to long-term morbidity. Decongestive
lymphatic therapy (DLT) is recognized as an optimal management strategy for patients with moderate
symptomatologies, but there is little data in regard to the most effective means of providing compression
therapy within a DLT protocol. We conducted a randomized trial of two forms of compression therapy
within the initial treatment phase of a DLT protocol for breast cancer-related lymphedema.
METHODS:
Subjects were required to have mild-moderate lymphedema (10-40% volume difference) acquired as a
result of curative breast cancer surgery and were randomized to compression bandaging or garments within
the initial treatment phase of a DLT protocol. Primary endpoint was change in affected limb volume assessed
via volumetry, and secondary endpoints were symptom control and upper extremity function assessed via
visual analogue scales and the Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire,
respectively. Endpoints were assessed at day 10 of treatment and at 3 months and compared to baseline.
RESULTS:
Twenty-one subjects were available for analysis. The group receiving bandaging experienced greater median
volume reductions at 10 days (70 vs. 5 mL; p = 0.387) and at 3 months (97.5 vs. 50 mL; p = 0.182). The
bandaging group also experienced a greater increase in median DASH scores at 10 days (+20.9 vs. +5; p =
0.143) and at 3 months (+18.4 vs. +3.3; p = 0.065).
CONCLUSION:
Within the initial treatment phase of a DLT protocol for acquired, breast cancer-related lymphedema,
compression bandaging may lead to greater volume reduction but worse upper extremity functional status
(higher DASH scores) as compared to compression garments.
PMID: 21553314 [PubMed - as supplied by publisher]
Int Orthop. 2011 May 7. [Epub ahead of print]
Reinfection after two-stage revision for periprosthetic infection of total knee arthroplasty.
Kubista B, Hartzler RU, Wood CM, Osmon DR, Hanssen AD, Lewallen DG.
Source
Department of Orthopedic Surgery, Mayo Clinic, Rochester, MN, USA, Bernd.Kubista@meduniwien.ac.at.
Abstract
PURPOSE:
Limited data exist regarding the long-term results or risk factors for failure after two-stage reimplantation for
periprosthetic knee infection. The purpose of this retrospective review was to investigate infection-free
implant survival and identify variables associated with reinfection after this procedure. Furthermore, a staging
system was evaluated as a possible prognostic tool for patients undergoing two-stage reimplantation of
infected total knee arthroplasty (TKA).
METHODS:
In this level II, retrospective prognostic study, 368 patients with infected TKA treated with a two-stage
revision protocol at our institution between 1998 and 2006 were reviewed. Patients who developed
recurrent infection and an equal number of patients randomly selected for the control group were analysed
for risk factors associated with treatment failure.
RESULTS:
At the most recent follow-up, 58 (15.8%) patients had developed reinfection after the two-stage
reimplantation. The median time to reinfection was 1,303 days (3.6 years), with follow-up time ranging from
six to 2,853 days (7.8 years). The strongest positive predictors of treatment failure included chronic
lymphoedema [hazard ratio (HR) = 2.28, 95% confidence interval (CI) 1.16-4.48; p = 0.02),and revision
between resection and definitive reimplantation (HR = 2.13, 95% CI 1.20-3.79; p = 0.01, whereas patients
treated with intravenously administered Cefazolin had a significant reduction in recurrent infection rate (HR =
0.48, 95% CI 0.25-0.90; p = 0.02).
CONCLUSIONS:
Our findings should be of help in counselling patients regarding their prognosis when faced with two-stage
exchange for infected TKA and provide a basis for future comparisons.
PMID: 21553042 [PubMed - as supplied by publisher]
May 18, 2011
Proc (Bayl Univ Med Cent). 2011 Apr;24(2):81-5.
The sensitivity and specificity of sentinel lymph node biopsy for breast cancer at Baylor University Medical
Center at Dallas: a retrospective review of 488 cases.
Shiller SM, Weir R, Pippen J, Punar M, Savino D.
Source
Department of Pathology (Shiller, Weir, Punar, Savino) and Oncology (Pippen), Baylor University Medical
Center at Dallas and Baylor Charles A. Sammons Cancer Center at Dallas. Dr. Shiller is now at the Mayo
Clinic, Rochester, Minnesota.
Abstract
Sentinel lymph node (SLN) biopsy has become the standard of care for breast carcinoma management, as it
precludes the negative morbid effects-including decreased shoulder range of motion, lymphedema, and
paresthesias-of unnecessary axillary lymph node dissection. However, the method of pathologic evaluation
of the lymph node has been scrutinized to obtain the greatest sensitivity, specificity, and negative predictive
value, ultimately for the benefit of the patient. This retrospective study analyzed 488 biopsies completed by
two surgeons and read by multiple pathologists affiliated with Pathologists Biomedical Laboratories. When
metastatic disease was not grossly obvious, analysis of the SLN began with touch imprint cytology and, if
necessary, a frozen section analysis. On the subsequent day, three levels of the SLN were analyzed with
hematoxylin and eosin stain and immunohistochemistry with cytokeratin AE1-3 and the appropriate control.
Touch imprint cytology and/or frozen section analysis (where applicable) correctly identified 78 of 89
macrometastases, with a sensitivity of 88%, specificity of 100%, and negative predictive value of 97%.
Sensitivity was 72% for micrometastases and 60% for isolated tumor cells, each with 100% specificity. In
conclusion, the sensitivity and specificity of SLN biopsy at our institution compares with the higher end of
percentages reported in the literature.
PMID: 21566748 [PubMed - in process] PMCID: PMC3069509
Jpn J Clin Oncol. 2011 May 12. [Epub ahead of print]
Exogenous VEGF-C Augments the Efficacy of Therapeutic Lymphangiogenesis Induced by Allogenic Bone
Marrow Stromal Cells in a Rabbit Model of Limb Secondary Lymphedema.
Zhou H, Wang M, Hou C, Jin X, Wu X.
Source
Department of Vascular Surgery, Shandong Provincial Hospital, Shandong University, Jinan, Shandong
Province, China.
Abstract
OBJECTIVE:
To determine the effect of bone marrow stromal cells transplantation and vascular endothelial growth factor
C administration as a treatment for secondary lymphedema.
METHODS:
Bone marrow stromal cells and/or vascular endothelial growth factor C protein were injected into a rabbit
model of limb lymphedema. Water displacement volumetry was performed to measure limb volume changes.
Immunohistochemistry was performed to detect VEGFR-3 and to count lymph vessel. Western blot analysis
was performed to detect vascular endothelial growth factor C.
RESULTS:
Before treatment, rabbits had an average volume of edema in the limb of 61.25 ± 5.28, 62.37 ± 4.97,
60.58 ± 7.18 and 61.79 ± 4.33 ml (P = 0.753), respectively, in the BMSC + VEGF-C, bone marrow
stromal cell, vascular endothelial growth factor C and control groups. With therapy, this was reduced to an
average volume of 7.60 ± 3.02, 12.78 ± 3.41, 31.55 ± 3.51 and 62.33 ± 6.59 ml, respectively, in the four
groups 6 months after treatment. Quantitative analysis showed that the vessel numbers were significantly
increased in the BMSC + VEGF-C, bone marrow stromal cell and vascular endothelial growth factor C
groups compared with the control group at 28 days after the operation (P< 0.05). Western blot analysis
demonstrated that expression of vascular endothelial growth factor C was higher in the BMSC + VEGF-C
and BMSC groups.
CONCLUSIONS:
The combined treatment with bone marrow stromal cell transplantation and vascular endothelial growth
factor C administration is superior to bone marrow stromal cell transplantation alone in the treatment of limb
lymphedema. Bone marrow stromal cell transplantation and vascular endothelial growth factor C
administration could enhance the therapeutic effect of each other.
PMID: 21565926 [PubMed - as supplied by publisher]
Br J Dermatol. 2011 Feb 24. doi: 10.1111/j.1365-2133.2011.10275.x. [Epub ahead of print]
Severe lower limb cellulitis is best diagnosed by dermatologists and managed with shared care between
primary and secondary care.
Levell NJ, Wingfield CG, Garioch JJ.
Source
Dermatology Department, Norfolk and Norwich University Hospital, Norwich NR4 7UY, U.K.
Abstract
Summary Background Cellulitis is responsible for over 400 000 bed days per year in the English
National Health Service (NHS) at the cost of £96 million. Objectives An audit following transfer of care of
lower limb cellulitis managed in secondary care from general physicians to dermatologists. Methods
Review of patient details and work diaries from the first 40 months of implementation of the new model of
care. Results Of 635 patients referred with lower limb cellulitis 33% had other diagnoses which did not
require admission. Four hundred and seven of 425 patients with cellulitis were managed entirely as
outpatients, many at home. Twenty-eight per cent of patients with cellulitis had an underlying skin disease
identified and treated, which is likely to have reduced the risk of recurrent cellulitis, leg ulceration and
lymphoedema. Only 18 of 635 patients referred with lower limb cellulitis required hospital admission for
conventional treatment. Conclusions This new way of managing suspected lower limb cellulitis offered
substantial savings for the NHS, and benefits of early and accurate diagnosis with correct home treatment
for patients.
© 2011 The Authors. BJD © 2011 British Association of Dermatologists 2011.
PMID: 21564054 [PubMed - as supplied by publisher]
Cochrane Database Syst Rev. 2011 May 11;5:CD002224.
Primary groin irradiation versus primary groin surgery for early vulvar cancer.
van der Velden J, Fons G, Lawrie TA.
Source
Department of Obstetrics and Gynaecology, Academic Medical Centre, PO Box 22660, Meibergdreef 9,
Amsterdam, Netherlands, 1105 AZ.
Abstract
BACKGROUND:
Despite changes in technique, morbidity after surgery for vulvar cancer is high and mainly related to the groin
dissection. Primary radiotherapy to the groin is expected to result in lower morbidity. However, studies on
the efficacy of primary radiotherapy to the groin in terms of groin recurrences and survival show conflicting
results.
OBJECTIVES:
To determine whether the effectiveness and safety of primary radiotherapy to the inguinofemoral lymph
nodes in early vulvar cancer is comparable with surgery.
SEARCH STRATEGY:
We searched The Cochrane Gynaecological Cancer Group Specialised Register, Cochrane Central Register
of Controlled Trials (CENTRAL), MEDLINE and EMBASE from 1966 to July 2010.
SELECTION CRITERIA:
We selected randomised clinical trials (RCTs) comparing inguinofemoral lymph node dissection and primary
radiotherapy of the inguinofemoral lymph nodes for patients with early squamous cell cancer of the vulva.
DATA COLLECTION AND ANALYSIS:
Two reviewers independently assessed study quality and extracted results. Primary outcome measures were
the incidence of groin recurrences, patient survival and morbidity.
MAIN RESULTS:
No new RCTs were identified by the updated search. Out of twelve identified papers only one met the
selection criteria. From this one small RCT of 52 women, there was a trend towards increased groin
recurrence rates (relative risk (RR) 10.21, 95% confidence interval (CI) 0.59 to 175.78), lower disease-
specific survival rates (RR 3.70, 95% CI 0.87 to 15.80), less lymphoedema (RR 0.06, 95% CI 0.00 to
1.03) and fewer life-threatening cardiovascular complications (RR 0.08, 95% CI 0.00 to 1.45) in the
radiotherapy group. Primary surgery was associated with a longer hospital stay than primary groin irradiation
(RR 0.28, 95% CI 0.13 to 0.58).
AUTHORS' CONCLUSIONS:
Primary radiotherapy to the groin results in less morbidity but may be associated with a higher risk of groin
recurrence and decreased survival when compared with surgery. Due to the small numbers in this trial and
criticisms regarding the depth of radiotherapy applied, corroboration of these findings by larger RCTs using
a standardised radiotherapy method, is desirable. However, until better evidence is available, surgery should
be considered the first choice treatment for the groin nodes in women with vulvar cancer. Individual patients
not physically able to withstand surgery may be treated with primary radiotherapy.
PMID: 21563133 [PubMed - in process]
Breast Cancer Res Treat. 2011 May 12. [Epub ahead of print]
Does the effect of weight lifting on lymphedema following breast cancer differ by diagnostic method: results
from a randomized controlled trial.
Hayes SC, Speck RM, Reimet E, Stark A, Schmitz KH.
Source
Queensland University of Technology, School of Public Health, Institute of Biomedical Innovation, Brisbane,
Australia.
Abstract
The lymphedema diagnostic method used in descriptive or intervention studies may influence results found.
The purposes of this work were to compare baseline lymphedema prevalence in the physical activity and
lymphedema (PAL) trial cohort and to subsequently compare the effect of the weight-lifting intervention on
lymphedema, according to four standard diagnostic methods. The PAL trial was a randomized controlled
intervention study, involving 295 women who had previously been treated for breast cancer, and evaluated
the effect of 12 months of weight lifting on lymphedema status. Four diagnostic methods were used to
evaluate lymphedema outcomes: (i) interlimb volume difference through water displacement, (ii) interlimb size
difference through sum of arm circumferences, (iii) interlimb impedance ratio using bioimpedance
spectroscopy, and (iv) a validated self-report survey. Of the 295 women who participated in the PAL trial,
between 22 and 52% were considered to have lymphedema at baseline according to the four diagnostic
criteria used. No between-group differences were noted in the proportion of women who had a change in
interlimb volume, interlimb size, interlimb ratio, or survey score of ≥5, ≥5, ≥10%, and 1 unit, respectively
(cumulative incidence ratio at study end for each measure ranged between 0.6 and 0.8, with confidence
intervals spanning 1.0). The variation in proportions of women within the PAL trial considered to have
lymphoedema at baseline highlights the potential impact of the diagnostic criteria on population surveillance
regarding prevalence of this common morbidity of treatment. Importantly though, progressive weight lifting
was shown to be safe for women following breast cancer, even for those at risk or with lymphedema,
irrespective of the diagnostic criteria used.
PMID: 21562712 [PubMed - as supplied by publisher]
May 23, 2011
Ultrasound Obstet Gynecol. 2011 May 16. doi: 10.1002/uog.9048. [Epub ahead of print]
Experimental treatment of bilateral fetal chylothorax using in utero pleurodesis.
Yang YS, Ma GC, Shih JC, Chen CP, Chou CH, Yeh KT, Kuo SJ, Chen TH, Hwu WL, Lee TH, Chen
M.
Source
Department of Obstetrics and Gynecology, College of Medicine, and Hospital, National Taiwan University,
Taipei, Taiwan.
Abstract
OBJECTIVE:
The use and efficacy of in utero pleurodesis for experimental treatment of bilateral fetal chylothorax (FC)
were assessed.
METHODS:
A total of 78 fetuses with bilateral pleural effusion referred to three tertiary referral centers in Taiwan
between 2005 and 2009 were analyzed for the karyotype (by amniocentesis) and the lymphocyte ratio in
pleural effusion (by thoracocentesis). Of these, 49 (62.8%) fetuses with a normal karyotype were
recognized to be FC; in which, 45 accepted intrapleural injection with 0.1KE OK-432 per side per
treatment. The clinical (e.g. hydrops vs. no hydrops) and genetic (e.g. mutations in the reported
lymphedema-associated loci: VEGFR3, PTPN11, FOXC2, ITGA9) parameters, as well as outcomes of
the treatment were evaluated. Survival at 1 year of age was defined as long-term survival (LSR) in this study.
RESULTS:
The overall LSR was 35.6% (16/45). The LSR in non-hydropic and hydropic fetuses were 66.7% (12/18)
and 14.8% (4/27), respectively. The LSR further decreased to 29.4% (10/34) if we only included those
onset at second trimester and excluded those onset at third trimester. Notably, 29.6% (8/27) of hydropic
fetuses was found to have mutations in the four loci we examined.
CONCLUSION:
In non-hydropic FC cases, the OK-432 pleurodesis appeared to be an experimental alternative to the gold-
standard thoracoamniotic shunting in hospitals where such treatment is not available due to technical and
logistic reasons but in hydropic fetuses the proposed treatment is ineffective (15% survival versus 44-66%
with shunting according to previous reports). Copyright © 2011 ISUOG. Published by John Wiley & Sons,
Ltd.
Copyright © 2011 ISUOG. Published by John Wiley & Sons, Ltd.
PMID: 21584887 [PubMed - as supplied by publisher]
Lab Invest. 2011 May 16. [Epub ahead of print]
Role of COX-2 in lymphangiogenesis and restoration of lymphatic flow in secondary lymphedema.
Kashiwagi S, Hosono K, Suzuki T, Takeda A, Uchinuma E, Majima M.
Source
1] Department of Pharmacology, Kitasato University School of Medicine, Kanagawa, Japan [2]
Department of Plastic and Aesthetic Surgery, Kitasato University School of Medicine, Kanagawa, Japan.
Abstract
The pathophysiology of secondary lymphedema remains poorly understood. To clarify the roles of
cyclooxygenase (COX)-2 in enhancement of lymphangiogenesis during secondary lymphedema, we tested a
mouse tail model and evaluated the recurrence of lymph flow. To induce lymphedema, a circumferential
incision was made in the tail of anesthetized mice to sever the dermal lymphatic vessels. The maximum
diameters of the tails were measured weekly. We found that the diameters of the tails around the wounds
were markedly increased after surgery, and reached maximum size 2 weeks after wounding in mice without
a COX-2 inhibitor, celecoxib (Celecoxib-). Expression of COX-2 in wound granulation tissues was
markedly increased 1 week after surgery compared with unwounded naive control mice. In Celecoxib-,
recurrence of lymphatic flow in the wound granulation tissues was detected 3 weeks after surgical treatment.
In contrast, lymphatic flow was markedly suppressed in mice treated with celecoxib (Celecoxib+). Newly
formed lymphatic structures were identified in the granulation tissues formed at wounded lesions in
Celecoxib-, whereas those were markedly suppressed in Celecoxib+. Interstitial tissue pressures in the distal
areas of the tail wounds were markedly increased in Celecoxib+ with reduced expression of vascular
endothelial cell growth factor (VEGF)-C. F4/80-positive cells were accumulated to the wound granulation
tissues in Celecoxib-, and the accumulation of these cells was suppressed in Celecoxib+. Prostaglandin E(2)
(PGE(2)) upregulated the expressions of VEGF-A and VEGF-C in cultured macrophages, but not human
lymphatic microvascular endothelial cells. The present study therefore suggests that lymphangiogenesis,
together with recurrence of lymph flow after surgical induction of lymphedema, is upregulated by COX-2
possibly via generation of PGs.Laboratory Investigation advance online publication, 16 May 2011; doi:
10.1038/labinvest.2011.84.
PMID: 21577211 [PubMed - as supplied by publisher]
Phlebology. 2011 May 16. [Epub ahead of print]
Evaluation of lymph drainage using bioelectrical impedance of the body.
de Godoy JM, Valente FM, Azoubel LM, Godoy MF.
Source
* Department of Cardiology and Cardiovascular Surgery, Medicine School of São José do Rio Preto-
FAMERP, Research CNPq (National Council for Research and Development), Brazil.
Abstract
AIM:
The aim of this study was to investigate the effects of manual and mechanical lymph drainage on the
bioelectrical composition of body tissues of patients with lymphoedema of the lower limbs.
METHOD:
Twenty-one patients with lymphoedema of one leg were evaluated using single frequency bioelectrical
impedance with four electrodes (SF-BIA4) immediately before and after a combination of manual and
mechanical lymph drainage. Statistical analysis used the two-tailed paired t-test with an alpha error of 5%
being considered acceptable.
RESULTS:
On comparing the results before and after lymph drainage, statistically significant differences were identified
for both lymphoedematous and apparently healthy legs, but there were no significant differences in the
alterations caused by the treatment between the healthy and lymphoedematous limbs of the same patient.
CONCLUSION:
It was concluded that the association of manual and mechanical lymph drainage both modified the body
composition as identified by bioelectrical impedance, and reduced the oedema.
PMID: 21576705 [PubMed - as supplied by publisher]
J Cell Biol. 2011 May 16;193(4):607-18.
Lymphatic vascular morphogenesis in development, physiology, and disease.
Schulte-Merker S, Sabine A, Petrova TV.
Source
Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences, and University Medical Centre, 3584
CT Utrecht, Netherlands.
Abstract
The lymphatic vasculature constitutes a highly specialized part of the vascular system that is essential for the
maintenance of interstitial fluid balance, uptake of dietary fat, and immune response. Recently, there has
been an increased awareness of the importance of lymphatic vessels in many common pathological
conditions, such as tumor cell dissemination and chronic inflammation. Studies of embryonic development
and genetically engineered animal models coupled with the discovery of mutations underlying human
lymphedema syndromes have contributed to our understanding of mechanisms regulating normal and
pathological lymphatic morphogenesis. It is now crucial to use this knowledge for the development of novel
therapies for human diseases.
PMID: 21576390 [PubMed - in process]
Dermatol Surg. 2011 May 16. doi: 10.1111/j.1524-4725.2011.02002.x. [Epub ahead of print]
Prospective, Randomized, Controlled Trial Comparing a New Two-Component Compression System with
Inelastic Multicomponent Compression Bandages in the Treatment of Leg Lymphedema.
Lamprou DA, Damstra RJ, Partsch H.
Source
Department of Dermatology, Phlebology, and Lymphology, Nij Smellinghe Hospital, Drachten, The
Netherlands Private Practice, Vienna, Austria.
Abstract
BACKGROUND New, less-bulky, short-stretch compression bandages could be a valuable alternative in
the management of lymphedema of the leg. OBJECTIVE To compare the effectiveness of a two-component
compression (2CC) system in the treatment of leg lymphedema with that of the traditional treatment with
conventional inelastic multicomponent compression bandages (IMC). METHODS Thirty hospitalized
patients with moderate to severe unilateral lymphedema (stage II-III) of the leg were included. Patients were
divided in two groups; one (n=15) received a 2CC, and the other (n=15) received IMC. Primary outcome
was volume reduction of the affected leg; secondary outcome was loss of interface pressure. RESULTS
Median leg volumes before bandaging were 4,150 mL (2CC) and 4,360 mL (IMC). Median volume
reduction after 2 hours was 120 mL (2.9%) with the 2CC system and 80 mL (1.8%) with IMC (p>.
05). After 24 hours, volume reduction was 8.4% and 4.4% respectively (p>.05). Interface pressure
dropped significantly within 2 hours of bandage application in both groups. CONCLUSION Our results
indicate that the 2CC system forms a suitable alternative to IMC in the conventional treatment of moderate
to severe lymphedema. This study was supported by a 3M Health Care grant to a foundation.
© 2011 by the American Society for Dermatologic Surgery, Inc.
PMID: 21575097 [PubMed - as supplied by publisher
J Am Acad Dermatol. 2011 Jun;64(6):1223-4.
Hidradenitis suppurativa complicated by severe lymphedema and lymphangiectasias.
Moosbrugger EA, Mutasim DF.
Source
Department of Dermatology, University of Cincinnati College of Medicine, Cincinnati, Ohio.
PMID: 21571207 [PubMed - in process]
Phlebology. 2011 May 16. [Epub ahead of print]
Evaluation of lymph drainage using bioelectrical impedance of the body.
de Godoy JM, Valente FM, Azoubel LM, Godoy MF.
Source
* Department of Cardiology and Cardiovascular Surgery, Medicine School of São José do Rio Preto-
FAMERP, Research CNPq (National Council for Research and Development), Brazil.
Abstract
AIM:
The aim of this study was to investigate the effects of manual and mechanical lymph drainage on the
bioelectrical composition of body tissues of patients with lymphoedema of the lower limbs.
METHOD:
Twenty-one patients with lymphoedema of one leg were evaluated using single frequency bioelectrical
impedance with four electrodes (SF-BIA4) immediately before and after a combination of manual and
mechanical lymph drainage. Statistical analysis used the two-tailed paired t-test with an alpha error of 5%
being considered acceptable.
RESULTS:
On comparing the results before and after lymph drainage, statistically significant differences were identified
for both lymphoedematous and apparently healthy legs, but there were no significant differences in the
alterations caused by the treatment between the healthy and lymphoedematous limbs of the same patient.
CONCLUSION:
It was concluded that the association of manual and mechanical lymph drainage both modified the body
composition as identified by bioelectrical impedance, and reduced the oedema.
PMID: 21576705 [PubMed - as supplied by publisher]
May 26, 2011
Clin Genet. 2011 May 19. doi: 10.1111/j.1399-0004.2011.01706.x. [Epub ahead of print]
Massively parallel sequencing and identification of genes for primary lymphoedema: a perfect fit.
Ostergaard P, Simpson M, Jeffery S.
Source
Medical Genetics Unit, Biomedical Sciences, St George's University of London, London, UK Division of
Genetics and Molecular Medicine, King's College London School of Medicine, Guy's Hospital, London,
UK.
Abstract
Ostergaard P, Simpson MA, Jeffery S. Massively parallel sequencing and the identification of genes for
primary lymphoedema: a perfect fit. Primary lymphoedema is a clinically and genetically heterogeneous
group of disorders characterized by disruption of the lymphatic system. To date, the majority of the
causative genes in primary lymphoedema have been identified through linkage analysis in large families with
multiple affected subjects. Studies aimed at isolating additional genes responsible for primary lymphoedema
have been hampered by cohorts comprised primarily of sporadic cases and small affected kindreds. In the
absence of genetic heterogeneity, recent development of massively parallel DNA sequencing technology,
specifically exome sequencing, has provided novel paradigms for disease gene identification in such cohorts.
In this review, we summarize the novel approaches to disease gene discovery with massively parallel
sequencing also known as Next Generation Sequencing (NGS), and show how the selection of unrelated
affected cases from clinically homogenous phenotypic subclassifications is proving to be a successful
approach for disease gene discovery in primary lymphoedema.
© 2011 John Wiley & Sons A/S.
PMID: 21595654 [PubMed - as supplied by publisher
Vojnosanit Pregl. 2011 Mar;68(3):270-3.
[Congenital intestinal lymphangiectasia].
[Article in Serbian]
Popović DD, Spuran M, Alempijević T, Krstić M, Djuranović S, Kovacević N, Damnjanović S, Micev M.
Source
Klinicki centar Srbije, Sluzba za patohistologiju, Beograd, Srbija. dr.popovic@sezampro.rs
Abstract
BACKGROUND:
Congenital intestinal lymphangiectasia is a disease which leads to protein losing enteropathy. Tortuous,
dilated lymphatic vessels in the intestinal wall and mesenterium are typical features of the disease. Clinical
manifestations include malabsorption, diarrhea, steatorrhea, edema and effusions. Specific diet and
medication are required for disease control.
CASE REPORT:
A 19-year old male patient was hospitalized due to diarrhea, abdominal swelling, weariness and fatigue.
Physical examination revealed growth impairment, ascites, and lymphedema of the right hand and forearm.
Laboratory assessment indicated iron deficiency anaemia, lymphopenia, malabsorption, inflammatory
syndrome, and urinary infection. Enteroscopy and video capsule endoscopy demonstrated dilated lymphatic
vessels in the small intestine. The diagnosis was confirmed by intestinal biopsy. The patient was put on high-
protein diet containing medium-chain fatty acids, somatotropin and supportive therapy.
CONCLUSION:
Congenital intestinal lymphangiectasia is a rare disease, usually diagnosed in childhood. Early recognition of
the disease and adequate treatment can prevent development of various complications.
PMID: 21526555 [PubMed - in process
Clin Radiol. 2011 Apr 23. [Epub ahead of print]
Regional diagnosis of lymphoedema and selection of sites for lymphaticovenular anastomosis using
elastography.
Mihara M, Hayashi Y, Murai N, Moriguchi H, Iida T, Hara H, Todokoro T, Narushima M, Uchida G,
Koshima I.
Source
Department of Plastic Surgery and Reconstructive Surgery, The University of Tokyo, Tokyo.
Abstract
AIM:
To evaluate the use of ultrasound elastography as a basis for determining the most appropriate sites for
lymphaticovenular anastomosis (LVA) for treatment of lymphoedema.
MATERIALS AND METHODS:
Preoperative elastography and LVA were performed in 11 patients (11 legs) with leg lymphoedema,
including two cases of primary oedema and nine of secondary oedema.
RESULTS:
The mean number of LVAs applied per leg was 4.4 (range 3-7). The mean reduction in the leg
circumference was 91.7%, and 10 of the 11 cases (90.0%) were improved. Hardness was reduced from a
mean of 1.6 before surgery to 0.9 after surgery, and improvement was also noted in 10 cases (90.9%). The
severity of oedema was determined in five regions in each leg, and was classified as elastography stage (ES)
0 in 11 regions, ES1 in 23, ES2 in 15, and ES3 in six.
CONCLUSIONS:
These results demonstrate the value of ultrasound elastography for the diagnosis of early-stage
lymphoedema and determination of LVA sites. This is the first report of diagnosis of lymphoedema using
elastography and the findings suggest that this procedure followed by LVA could be used as a new
therapeutic method for early-stage lymphoedema.
Copyright © 2011 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.
PMID: 21524415 [PubMed - as supplied by publisher]
Arch Phys Med Rehabil. 2011 May;92(5):756-764.e1.
Assessment of lymphatic contractile function after manual lymphatic drainage using near-infrared
fluorescence imaging.
Tan IC, Maus EA, Rasmussen JC, Marshall MV, Adams KE, Fife CE, Smith LA, Chan W, Sevick-
Muraca EM.
Source
Center for Molecular Imaging, The Brown Foundation Institute of Molecular Medicine, The University of
Texas Health Science Center, Houston, TX; Formerly, Department of Radiology, Baylor College of
Medicine, Houston, TX.
Abstract
Tan I-C, Maus EA, Rasmussen LC, Marshall MV, Adams KE, Fife CE, Smith LA, Chan W, Sevick-
Muraca EM. Assessment of lymphatic contractile function after manual lymphatic drainage using near-
infrared fluorescence imaging.
OBJECTIVE:
To investigate the feasibility of assessing the efficacy of manual lymphatic drainage (MLD), a method for
lymphedema (LE) management, by using near-infrared (NIR) fluorescence imaging.
DESIGN:
Exploratory pilot study.
SETTING:
Primary care unit.
PARTICIPANTS:
Subjects (N=10; age, 18-68y) with a diagnosis of grade I or II LE and 12 healthy control subjects (age, 22-
59y).
INTERVENTION:
Indocyanine green (25 μg in 0.1 mL each) was injected intradermally in bilateral arms or legs of subjects.
Diffused excitation light illuminated the limbs, and NIR fluorescence images were collected by using custom-
built imaging systems. Subjects received MLD therapy, and imaging was performed pre- and posttherapy.
MAIN OUTCOME MEASURES:
Apparent lymph velocities and periods between lymphatic propulsion events were computed from
fluorescence images. Data collected pre- and post-MLD were compared and evaluated for differences.
RESULTS:
By comparing pre-MLD lymphatic contractile function against post-MLD lymphatic function, results showed
that average apparent lymph velocity increased in both the symptomatic (+23%) and asymptomatic (+25%)
limbs of subjects with LE and control limbs (+28%) of healthy subjects. The average lymphatic propulsion
period decreased in symptomatic (-9%) and asymptomatic (-20%) limbs of subjects with LE, as well as in
control limbs (-23%).
CONCLUSIONS:
We showed that NIR fluorescence imaging could be used to quantify immediate improvement of lymphatic
contractile function after MLD.
Copyright © 2011 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights
reserved.
PMID: 21530723 [PubMed - in process]
May 10, 2011
3,7-bis(dimethylamino)-phenothiazin-5-ium chloride.
Authors
Chopra A.
Source
Molecular Imaging and Contrast Agent Database (MICAD) [Internet]. Bethesda (MD): National Center for
Biotechnology Information (US); 2004-2011.
2011 Apr 05 [updated 2011 Apr 29].
Excerpt
A sentinel lymph node (SLN)is the first lymph node showing presence of metastasized cancer cells from a
tumor. An SLN biopsy (SLNB) is the method of choice to stage breast cancer (i.e., to describe the stage of
cancer progress using numbers I to IV, going from low to highest progression) in patients exhibiting clinically
negative (i.e., without metastases) axillary lymph nodes (1, 2). Once detected and confirmed, the metastatic
spread of the cancer from the primary tumor to the axillary lymph nodes through the lymphatic system is then
tracked with either a radiolabeled sulfur colloid and/or a blue dye (isosulfan blue or methylene blue; neither
of these dyes are approved by the United States Food and Drug Administration (FDA) for this application)
(2). After visual confirmation, the SLN is surgically resected, and the definitive presence of cancer is
established with histological methods. Although the SLNB procedure is minimally invasive, it has a 5%–10%
false negative rate of detecting cancer and can possibly lead to lymphedema, seroma formation (collection of
fluid under the skin), injury to local sensory nerves, and a reduction in the patient's range of motion (1, 2). In
some cases, ultrasonography (US), which is the detection of high frequency sound waves, is used to identify
a SLN, and a biopsy is obtained with a fine-needle aspiration biopsy (FNAB). The biopsy sample is then
subjected to molecular analysis using the real-time reverse transcription-polymerase chain reaction to detect
cancer in the tissue from the breast. A limitation of using US to identify a SLN is that it can only determine
the size and shape of the lymph node but cannot specifically distinguish between a cancerous and a non-
cancerous lymph node; this limitation reduces the sensitivity of the FNAB procedure to detect a malignancy
(3). Photoacoustic imaging (PAI) is a noninvasive method that does not involve the use of ionizing radiation
for the detection of cancer. This technique, which uses a combination of the optical and US imaging
modalities to detect malignant lesions, angiogenesis, etc (4), has been described in detail elsewhere (5). In
brief, application of a pulse of light to biological tissue results in the generation of ultrasonic waves
(photoacoustic waves) due to the thermoelastic expansion and contraction of the tissue (i.e., a fraction of the
light is converted into heat within the tissue). Subsequently, the photoacoustic waves are captured with a
suitable device (transducer) that captures the US waves and converts them into an image. If used by itself,
optical imaging has a limited imaging depth and spatial resolution because light is scattered by the tissue. As
a result, images generated with US alone have a low contrast and are speckled (5). The main advantage of
using PAI is that the depth and resolution of an image can be improved by controlling the detection
frequency of the transducer, and the quality of the images can be further enhanced by using intrinsic contrast
agents (e.g., melanin and hemoglobin) or exogenous contrast agents (e.g., an organic dye such as methylene
blue, nanoparticles, etc.) (5). Methylene blue is an aromatic compound that has many applications in biology
and medicine. In the laboratory, methylene blue is often used to stain blood cells for histological
investigations, to detect nucleic acids on blots, and to determine the viability of yeast cells. Although
methylene blue is not approved for clinical use by the FDA, it is available commercially in the United States
for off label use as an intravenous injection to treat methemoglobinemia. Methylene blue is also under
investigation in clinical trials to treat osteoarthritis, to detect invasive aspergillosis, and to map and localize
SLN in breast and thyroid cancer patients. In several European countries, a procedure using methylene blue
has been approved to reduce the pathogen load (e.g., viruses such as HIV and hepatitis B and C) in
individual units of human plasma to be used for transfusion purposes (6). It has been shown that methylene
blue radiolabeled with astatine-211 is suitable for the diagnosis and selective treatment of melanoma in mice
(7). Investigators have also shown that methylene blue encapsulated in nanoparticles can be used for in vivo
imaging and photodynamic therapy in mice (exposure of methylene blue nanoparticles to high-energy light
pulses results in the production of nascent oxygen that damages the nucleic acids in the cells) (8). Recently,
in an effort to develop an alternative method to SLNB and FNAB for the detection of SLNs in breast
cancer patients, methylene blue has been successfully used as a contrast agent to visualize SLN in rats with
PAI (1, 2).
Sections
Background
Synthesis
In Vitro Studies: Testing in Cells and Tissues
Animal Studies
Human Studies
Supplemental Information
NIH Support
References
PMID: 21542554 [PubMed)}
May 11, 2011
Ann Plast Surg. 2011 May 2. [Epub ahead of print]
Vascularized Lymph Node Transfer Based on the Hilar Perforators Improves the Outcome in Upper Limb
Lymphedema.
Gharb BB, Rampazzo A, di Spilimbergo SS, Xu ES, Chung KP, Chen HC.
Source
From the *Plastic Surgery Department, China Medical University Hospital, Taichung, Taiwan; and
†Department of Public Health, Institute of Health Care Organization Administration, College of Public
Health, National Taiwan University, Taipei, Taiwan.
Abstract
BACKGROUND:
Maintenance of the blood supply to the lymph nodes is necessary for survival and function. We report the
outcome of vascularized lymph node transfer with hilar perforators compared with the conventional
technique.
PATIENTS:
A total of 21 patients affected by early stage II upper limb lymphedema were included in this study. Of
them, 11 patients received a free groin flap containing lymph nodes and 10 patients received vascularized
inguinal lymph nodes with hilar perforators. Mean follow-up was 46 and 40 months, respectively.
Complications, secondary procedures, circumference of the limb, and subjective symptomatology were
registered. The differences were evaluated statistically.
RESULTS:
The limb circumferences decreased significantly in the new group. The number of secondary procedures was
significantly higher in the standard group. There were 2 cases of partial flap loss and donor site lymphorrhea
in the standard group. In both the groups, visual analog scale scores improved after the operation.
CONCLUSIONS:
Transfer of vascularized inguinal lymph nodes based on the hilar perforators improves the outcomes in the
treatment of early lymphedema of the upper extremity.
PMID: 21540737 [PubMed - as supplied by publisher]
Commun Agric Appl Biol Sci. 2011;76(1):189-92.
Assessment of skinfold thickness as a factor related to chronic progressive lymphoedema in Belgian draught
horses.
De Keyser K, Peeters LM, Buys N, Janssens S.
Source
Laboratory of Livestock Genetics, Department of Biosystems, K.U.Leuven, Kasteelpark Arenberg 30, bus
2456, 3001 Leuven, Belgium.
PMID: 21539228 [PubMed - in process]
Ann Surg Oncol. 2011 May 3. [Epub ahead of print]
Therapeutic Surgical Management of Palpable Melanoma Groin Metastases: Superficial or Combined
Superficial and Deep Groin Lymph Node Dissection.
van der Ploeg AP, van Akkooi AC, Schmitz PI, van Geel AN, de Wilt JH, Eggermont AM, Verhoef C.
Source
Department of Surgical Oncology, Erasmus University Medical Center - Daniel den Hoed Cancer Center,
Rotterdam, The Netherlands.
Abstract
BACKGROUND:
Management of patients with clinically detectable lymph node metastasis to the groin is by ilioinguinal or
combined superficial and deep groin dissection (CGD) according to most literature, but in practice
superficial groin dissection (SGD) only is still performed in some centers. The aim of this study is to evaluate
the experience in CGD versus SGD patients in our center.
METHODS:
Between 1991 and 2009, 121 therapeutic CGD and 48 SGD were performed in 169 melanoma patients
with palpable groin metastases at our institute. Median follow-up was 20 and, for survivors, 45 months.
RESULTS:
In this heterogeneous group of patients, overall (OS) and disease-free survival, local control rates, and
morbidity rates were not significantly different between CGD and SGD patients. However, CGD patients
had a trend towards more chronic lymphedema. Superficial lymph node ratio, the number of positive
superficial lymph nodes, and the presence of deep nodes were prognostic factors for survival. CGD patients
with involved deep lymph nodes (24.8%) had estimated 5-year OS of 12% compared with 40% with no
involved deep lymph nodes (p = 0.001). Preoperative computed tomography (CT) scan had high negative
predictive value of 91% for detection of pelvic nodal involvement.
CONCLUSIONS:
This study demonstrated that survival and local control do not differ for patients with palpable groin
metastases treated by CGD or SGD. Patients without pathological iliac nodes on CT might safely undergo
SGD, while CGD might be reserved for patients with multiple positive nodes on SGD and/or positive deep
nodes on CT scan.
PMID: 21537867 [PubMed - as supplied by publisher]
Br J Nurs. 2011 Apr 14-27;20(7):418, 420, 422.
Use of compression hosiery in chronic oedema and lymphoedema.
Lay-Flurrie K.
Source
St Albans City Hospital.
Abstract
The management of chronic oedema is a continuing partnership between patient and practitioner and
accurate diagnosis and treatment planning are essential to control the condition in order to prevent
complications and optimise the patient's quality of life. A paucity of funding, lack of knowledge and
confidence on the part of practitioners and widely varying access to services means that many patients face
barriers to gaining appropriate treatment. Nurses in many spheres will come across patients with some form
of chronic oedema. The following article describes the types and causes of chronic oedema and
lymphoedema and explores the use of compression hosiery as one facet in management of the condition.
Patient education and the role of the practitioner are also highlighted to develop awareness of the need for
adequate preparation of a patient to facilitate concordance and self-management of their condition.
PMID: 21537258 [PubMed - in process]
Plast Reconstr Surg. 2011 May;127(5):1987-92.
Lambda-shaped anastomosis with intravascular stenting method for safe and effective lymphaticovenular
anastomosis.
Yamamoto T, Narushima M, Kikuchi K, Yoshimatsu H, Todokoro T, Mihara M, Koshima I.
Source
Tokyo, Japan From the Department of Plastic and Reconstructive Surgery, Graduate School of Medicine,
University of Tokyo.
Abstract
BACKGROUND:
: Lymphaticovenular anastomosis has become an increasingly common treatment for lymphedema.
Supermicrosurgical techniques are essential for the successful performance of lymphaticovenular
anastomosis. A positive correlation between the number of lymphaticovenular anastomoses performed and
therapeutic efficacy has been reported, and in performing these anastomoses, the establishment of as many
bypasses as possible is important.
METHODS:
: Forty limbs of 20 patients with lower extremity lymphedema who underwent lymphaticovenular
anastomosis in our department were assessed. All cases were performed under local anesthesia using two to
four surgical microscopes. A new method of anastomosis, lambda-shaped anastomosis assisted by
intravascular stenting, was chosen in required cases.
RESULTS:
: Lymphaticovenular anastomoses resulted in 186 anastomoses on 20 patients with lower extremity
lymphedema; the average number of anastomoses per case was 9.3 (range, five to 18). The number of
surgical microscopes used ranged from two to four (average, 3.3), and the duration of the operation ranged
from 3 to 5 hours (average, 4.1). In the cases of lambda-shaped anastomosis (n = 11), the number of
anastomoses was significantly greater than in the cases without lambda-shaped anastomosis (n = 9; 10.2 ±
2.3 versus 8.2 ± 1.4; p < 0.05).
CONCLUSIONS:
: Lambda-shaped anastomosis assisted by intravascular stenting is a safe and relatively easy method that can
be performed by surgeons with less than 1 year of experience in microsurgery. This in turn allows efficient
lymphaticovenular anastomoses to be performed simultaneously by a team of surgeons, resulting in an
increased number of bypasses.
PMID: 21532425 [PubMed - in process]
Plast Reconstr Surg. 2011 May;127(5):1979-86.
Characteristic indocyanine green lymphography findings in lower extremity lymphedema: the generation of a
novel lymphedema severity staging system using dermal backflow patterns.
Yamamoto T, Narushima M, Doi K, Oshima A, Ogata F, Mihara M, Koshima I, Mundinger GS.
Source
Tokyo, Japan; and Baltimore, Md. From the Department of Plastic and Reconstructive Surgery, Graduate
School of Medicine, University of Tokyo, and Division of Plastic, Reconstructive, and Maxillofacial Surgery,
The Johns Hopkins Hospital.
Abstract
BACKGROUND:
: Indocyanine green lymphography has been a highly useful modality in the clinical examination and surgical
management of patients with lymphedema. No formal classification system of indocyanine green imaging
findings according to the severity of lymphedema exists, however. The purpose of this study was to
describe, analyze, and classify characteristic indocyanine green lymphography findings to uniformly guide
surgical management of lymphedema using this modality.
METHODS:
: Forty-five patients (78 limbs) with lower extremity lymphedema underwent indocyanine green
lymphography. All lymphography images were recorded in photographs and videos. Images were reviewed
and analyzed to classify characteristic findings according to clinical severity as determined by Campisi clinical
lymphedema staging.
RESULTS:
: Lymphography findings were classifiable into two patterns. Mild cases of lymphedema were characterized
by a linear lymphatic channel pattern (linear pattern). In more severe cases, lymphatic channels
demonstrated retrograde lymphatic flow (dermal backflow pattern) and diminution or absence of linear
channel patterning. Three dermal backflow patterns, splash, stardust, and diffuse, were identified and
correlated with the progression of lymphedema severity. These findings supported the generation of a novel
anatomical lymphedema severity staging system, the dermal backflow staging system.
CONCLUSIONS:
: Indocyanine green lymphography is a safe, minimally invasive, and useful tool for the surgical evaluation of
extremity lymphedema. Characteristic indocyanine green lymphography patterns are consistent and correlate
with clinical severity. The dermal backflow staging system can facilitate patient stratification, discussion
between referring parties, and surgical planning.
PMID: 21532424 [PubMed - in process]
Plast Reconstr Surg. 2011 May;127(5):1804-11.
Microsurgical lymphaticovenous implantation targeting dermal lymphatic backflow using indocyanine green
fluorescence lymphography in the treatment of postmastectomy lymphedema.
Furukawa H, Osawa M, Saito A, Hayashi T, Funayama E, Oyama A, Sekido M, Yamamoto Y.
Source
Sapporo, Japan From the Department of Plastic and Reconstructive Surgery, Graduate School of Medicine,
University of Hokkaido at Sapporo.
Abstract
BACKGROUND:
: Microsurgical lymphaticovenous implantation in lymphedema is done to create a lymphaticovenous shunt by
an implantation of collecting lymphatics into the small vein, as reported previously. The authors have recently
introduced ultrasonograpy and indocyanine green fluorescence lymphography into this procedure.
METHODS:
: Nine cases of postmastectomy lymphedema had received preoperative venous marking using
ultrasonography and lymphatic mapping using indocyanine green fluorescence lymphography. The concept
of modification is to pick up the most effective point for microsurgical lymphaticovenous implantation that
involves both subcutaneous veins and the dermal backflow of excess lymphatics. Objective improvement
was analyzed by the percent reduction of edema circumference at two points of the affected forearm.
RESULTS:
: Preoperative lymphography showed a spotty image for dermal backflow in all nine extremities, a linear
image on the dorsal hand in six extremities, and a linear image on the forearm in three extremities. With an
average follow-up of 17 months, three patients had excellent results with the reduction of edema
circumference more than 50 percent for both the distal and proximal sites of the treated forearm. Four
patients had good results with the reduction of edema circumference more than 50 percent at the distal or
proximal sites, two patients had fair results, and no patients had poor results. The average number of
modified microsurgical lymphaticovenous implantations was 3.7 per case.
CONCLUSION:
: Modified microsurgical lymphaticovenous implantation is expected to provide favorable results with a
minimum number of these modified implantations, even though no linear lymph channel was detected by
preoperative indocyanine green fluorescence lymphography.
PMID: 21532410 [PubMed - in process]
Arch Phys Med Rehabil. 2011 May;92(5):756-764.e1
Assessment of lymphatic contractile function after manual lymphatic drainage using near-infrared
fluorescence imaging.
Tan IC, Maus EA, Rasmussen JC, Marshall MV, Adams KE, Fife CE, Smith LA, Chan W, Sevick-
Muraca EM.
Source
Center for Molecular Imaging, The Brown Foundation Institute of Molecular Medicine, The University of
Texas Health Science Center, Houston, TX; Formerly, Department of Radiology, Baylor College of
Medicine, Houston, TX
.
Abstract
Tan I-C, Maus EA, Rasmussen LC, Marshall MV, Adams KE, Fife CE, Smith LA, Chan W, Sevick-
Muraca EM. Assessment of lymphatic contractile function after manual lymphatic drainage using near-
infrared fluorescence imaging.
OBJECTIVE:
To investigate the feasibility of assessing the efficacy of manual lymphatic drainage (MLD), a method for
lymphedema (LE) management, by using near-infrared (NIR) fluorescence imaging.
DESIGN:
Exploratory pilot study.
SETTING:
Primary care unit.
PARTICIPANTS:
Subjects (N=10; age, 18-68y) with a diagnosis of grade I or II LE and 12 healthy control subjects (age, 22-
59y).
INTERVENTION:
Indocyanine green (25 μg in 0.1 mL each) was injected intradermally in bilateral arms or legs of subjects.
Diffused excitation light illuminated the limbs, and NIR fluorescence images were collected by using custom-
built imaging systems. Subjects received MLD therapy, and imaging was performed pre- and posttherapy.
MAIN OUTCOME MEASURES:
Apparent lymph velocities and periods between lymphatic propulsion events were computed from
fluorescence images. Data collected pre- and post-MLD were compared and evaluated for differences.
RESULTS:
By comparing pre-MLD lymphatic contractile function against post-MLD lymphatic function, results showed
that average apparent lymph velocity increased in both the symptomatic (+23%) and asymptomatic (+25%)
limbs of subjects with LE and control limbs (+28%) of healthy subjects. The average lymphatic propulsion
period decreased in symptomatic (-9%) and asymptomatic (-20%) limbs of subjects with LE, as well as in
control limbs (-23%).
CONCLUSIONS:
We showed that NIR fluorescence imaging could be used to quantify immediate improvement of lymphatic
contractile function after MLD.
Copyright © 2011 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights
reserved.
PMID: 21530723 [PubMed - in process]
MED NEWS FORMATTED DOCS (2) :
May 4, 2011
Lymphoseek(R) (Tilmanocept) Meets All Endpoints In Neo3-09 Phase 3 Study
Neoprobe Corporation (NYSE Amex: NEOP), a diversified developer of innovative oncology diagnostic
products, today announced top-line results from its Lymphoseek(R) (tilmanocept) NEO3-09 study. The
NEO3-09 study met all primary and secondary endpoints and highlighted the superior performance by
Lymphoseek compared to vital blue dye in intraoperative lymphatic mapping (ILM), a procedure in which
lymph nodes are identified for biopsy to assess for the presence of tumor. The NEO3-09 Phase 3 clinical
study, the Company's second successful Phase 3 study for Lymphoseek, enrolled over 150 subjects with
either breast cancer or melanoma within the intent-to-treat (ITT) population. Lymphoseek performed
equally well in both cancer types. As previously disclosed by the Company, the full NEO3-09 data set will
be presented at the 2011 Annual Meeting of the American Society of Clinical Oncology, June 3-7, in
Chicago.
"The results from NEO3-09 are important not only in that they demonstrate that Lymphoseek is safe and
well-tolerated but in many ways that it is a clinically superior lymphatic mapping agent to vital blue dye," said
Dr. Vernon K. Sondak, Chief of the Division of Cutaneous Oncology at the H. Lee Moffitt Cancer Center
and Research Institute. "Currently, vital blue dyes like isosulfan blue are the only FDA-approved agents for
ILM. These blue dyes are helpful, but have significant limitations. Lymphoseek provided clinically meaningful
advantages over the blue dyes and I believe it will be a useful agent in ILM."
The primary endpoint of this study was the comparison, or concordance rate, of Lymphoseek versus vital
blue dye in ILM, where vital blue dye was designated as the "Truth Standard" comparator. NEO3-09 study
subjects yielded over 200 lymph nodes stained with vital blue dye. Of the vital blue dye stained nodes,
Lymphoseek detected all of them, a concordance rate of 100%, which is highly statistically significant. This
concordance rate was consistent with the rate observed in the NEO3-05 Phase 3 study of approximately
98%, which also was highly statistically significant.
Using Lymphoseek as the Truth Standard, the reverse concordance rate for vital blue dye was
approximately 60%, a finding similar to the retrospective reverse concordance rate observed in the NEO3-
05 Phase 3 study of approximately 69%. These data demonstrate that in these studies vital blue dye
statistically was not equivalent to, and in fact was inferior to, Lymphoseek in this measure of lymph node
detection.
Use of the concordance data and reverse concordance data in a pre-specified, prospective test of
superiority showed that Lymphoseek's performance was statistically superior to vital blue dye in lymph node
detection.
Lymphoseek also demonstrated a superior ability to detect lymph nodes that contained cancer. In NEO3-
09, the ILM procedures found pathology-confirmed, cancer-positive lymph nodes at a rate consistent with
the general rate of nodal involvement typically observed in these cancer types. Of these pathology-
confirmed, cancer-positive nodes, Lymphoseek detected all of them, for a failed detection rate of 0%. In
contrast, vital blue missed over 25% of cancer-positive nodes. This prospective analysis confirmed the
lower failed detection rate for Lymphoseek observed retrospectively in the NEO3-05 Phase 3 study.
Lymphoseek's substantially lower failed detection rate means that it missed fewer lymph nodes containing
cancer, a key finding given that the objective of ILM is to determine if the cancer has spread to the lymph
nodes.
In both NEO3-09 and NEO3-05, Lymphoseek demonstrated no drug-related serious adverse events or
clinically significant adverse events, whereas vital blue dye showed several significant drug-related adverse
events. In over 500 subjects receiving Lymphoseek to date, no clinically significant drug-related adverse
events have been reported.
In a full regional lymph node dissection procedure, a patient with breast cancer or melanoma may have as
many as 20 to 30 lymph nodes removed in order to determine whether or not cancer has spread to other
parts of their body. This very invasive procedure frequently causes significant side effects. In the NEO3-05
and NEO3-09 studies combined, Lymphoseek detected an average of 2.4 lymph nodes per patient,
whereas vital blue dye detected a similar average of approximately 1.5 lymph nodes per patient. With this
relatively small difference in number of nodes removed, Lymphoseek exhibited superior performance in
detecting lymph nodes containing cancer, as evidenced by its lower failed detection rate noted above. The
average number of lymph nodes detected by Lymphoseek in a much less invasive manner is still far below
the number of lymph nodes removed in full regional node dissection procedures, thus potentially sparing the
patient the morbidity and side effects commonly associated with more complete regional nodal dissection
procedures.
"The NEO3-09 Phase 3 study met its endpoints and confirmed the previous findings of high concordance
and superiority demonstrated in the first Phase 3 study, NEO3-05," said Dr. Fred Cope, Neoprobe's
Senior Vice President, Pharmaceutical Research and Clinical Development. "Lymphoseek also showed
superiority in detecting lymph nodes that contained tumor. This is important because detecting lymph nodes
bearing tumor is the underlying reason for performing ILM procedures to enable lymph-node biopsy."
"In clinical studies, Lymphoseek has been shown to be a safe and effective tool for superior detection of
lymph nodes and offers an enhanced ability to accurately identify nodes with a high potential of tumor
metastases" stated Dr. Mark Pykett, Neoprobe's President and CEO. "This results in lower failed detection
rates than the current standard approach in intraoperative lymphatic mapping using vital blue dye. With these
encouraging data, our plans are on track to submit the Lymphoseek New Drug Application to the FDA in
the third quarter."
About Lymphoseek
Lymphoseek is a proprietary radioactive diagnostic tracing agent being developed for use in connection with
gamma detection devices in a surgical procedure known as Intraoperative Lymphatic Mapping. Two Phase
3 multi-center clinical trials (clinicaltrials.gov, trial registration numbers NCT00671918 and NCT01106040)
for Lymphoseek in patients with breast cancer or melanoma have concluded. A third Phase 3 clinical study
to evaluate the efficacy of Lymphoseek as a sentinel lymph node tracing agent in patients with head and neck
squamous cell carcinoma is currently ongoing (clinicaltrials.gov, trial registration number NCT00911326).
May 5, 2011
Survivors Of Childhood Cancer Are At Increased Risk For Ongoing Post-Therapy GI Complications
Patients who received therapy for cancer during childhood have an increased risk of developing
gastrointestinal (GI) complications later in life, according to a new study in Gastroenterology, the official
journal of the American Gastroenterological Association (AGA) Institute. Compared with their siblings,
cancer survivors had an increased risk of late-onset complications of the upper GI tract, lower GI tract and
liver.
"Survivors are at elevated risk for ongoing gastrointestinal complications after therapy," said Robert
Goldsby, MD, of the University of California, San Francisco Children's Hospital and lead author of the
study. "Because these gastrointestinal complications may impact quality of life, health-care providers should
be aware of potential gastrointestinal problems in this population as they evaluate acute symptoms and plan
ongoing follow-up care."
As more children diagnosed with cancer are surviving long-term, it is increasingly important to recognize the
long-term consequences of their cancer and its therapy. This analysis shows that survivors of childhood
cancer have a higher incidence of self-reported GI complaints compared with their siblings. Risks for
colostomy/ileostomy, cirrhosis or liver biopsy were highest. Older age at diagnosis, exposure to abdominal
radiation and certain chemotherapy treatments increase that risk. More than 40 percent of childhood cancer
survivors reported a late GI complication by 20 years after cancer therapy. The probability of experiencing a
late GI consequence was greater in survivors compared to siblings. The survivor's prior experience may
increase their sensitivity to GI-related symptoms, but cancer treatments may cause direct damage to the GI
organ system.
"The risks of late GI complications may change as therapy for childhood and adolescent cancer continues to
evolve and will require studies of more recently treated patients," added Dr. Goldsby. Although various
disease-specific combinations of chemotherapy, radiation and surgery have dramatically improved survival,
these treatment modalities have the potential to cause significant GI complications. For example, abdominal
radiation often results in several acute toxicities, including intestinal inflammation and abnormal movement of
the intestinal tract. Chemotherapy is associated with many acute GI toxicities, including nausea, vomiting,
diarrhea, constipation and increased susceptibility to GI infections. Intra-abdominal surgery and subsequent
GI complications are also contributors to GI toxicity of cancer therapy. Long-term GI consequences,
however, have not been extensively studied.
In this study, doctors evaluated the incidence of long-term GI outcomes and identified treatment-related risk
factors. The goals of this analysis were to describe the incidence of self-reported adverse GI conditions
occurring at least five years after diagnosis and to evaluate the effect of different treatment-associated factors
on the risk of developing these GI events.
Upper GI, lower GI and liver adverse outcomes were assessed in cases from participants in the Childhood
Cancer Survivor Study, a study of 14,358 survivors of childhood cancer (i.e., leukemias, brain tumors,
lymphomas, Wilms tumor, neuroblastoma, sarcomas and bone tumors) who were diagnosed between 1970
and 1986 at one of 26 collaborating institutions in the U.S. and Canada; data were compared with those
from randomly selected siblings. The median age at cancer diagnosis was 6.8 years, and the median age at
outcome assessment was 23.2 years for survivors and 26.6 years for siblings.
May 15, 2011
Cancer Nurs. 2011 May 9. [Epub ahead of print]
Voices From the Shadows: Living With Lymphedema.
Ridner SH, Bonner CM, Deng J, Sinclair VG.
Source
Author Affiliations: Vanderbilt University School of Nursing, Nashville, Tennessee.
Abstract
BACKGROUND:
Breast cancer survivors with lymphedema face a lifetime of stressful physical and emotional symptoms and
challenging self-care demands. An in-depth understanding of the perceptions and feelings surrounding life
with lymphedema is critical to developing effective supportive care approaches.
OBJECTIVE:
The objective of the study was to explore perceptions and feelings related to lymphedema in breast cancer
survivors.
METHOD:
The expressive writings of 39 individuals were evaluated for this descriptive qualitative study. Data were
analyzed using conventional content analysis.
RESULTS:
Qualitative analyses produced 4 major themes: (1) marginalization and minimization, (2) multiplying losses,
(3) yearning to return to normal, and (4) uplifting resources. Subthemes for each major theme were also
identified.
CONCLUSION:
The lymphedema experiences of breast cancer survivors reveal perceptions of marginalization from health
care providers who are not well informed about lymphedema management and minimizing its impact.
Multiple distressing losses confront these patients on a daily basis, including body image disturbances, loss of
functionality and control over time, permanent uncertainty, and adverse effects on relationships. The daily
challenges of lymphedema often result in cumulative frustration and resentment that contribute to failure to
perform self-care. Normalcy has been lost, never to return. These women find solace, encouragement, and
hope to meet the challenges of lymphedema through support from others and their spiritual beliefs.
IMPLICATIONS FOR PRACTICE:
Health care providers need greater awareness of the physical and psychosocial effects of lymphedema in
breast cancer survivors. Nurses have unique opportunities to serve as advocates for reducing perceived
marginalization and promoting effective self-care and other activities that promote psychological well-being
and reduce physical deterioration.
PMID: 21558848 [PubMed - as supplied by publisher]
Support Care Cancer. 2011 May 8. [Epub ahead of print]
Compression garments versus compression bandaging in decongestive lymphatic therapy for breast cancer-
related lymphedema: a randomized controlled trial.
King M, Deveaux A, White H, Rayson D.
Source
Occupational Therapy, Capital District Health Authority, Room 326, NS Rehabilitation Center, 1341
Summer Street, Halifax, NS, B3H 4KY, Canada, myrna.king@cdha.nshealth.ca.
Abstract
BACKGROUND:
Lymphedema as a result of curative surgery for breast cancer can lead to long-term morbidity. Decongestive
lymphatic therapy (DLT) is recognized as an optimal management strategy for patients with moderate
symptomatologies, but there is little data in regard to the most effective means of providing compression
therapy within a DLT protocol. We conducted a randomized trial of two forms of compression therapy
within the initial treatment phase of a DLT protocol for breast cancer-related lymphedema.
METHODS:
Subjects were required to have mild-moderate lymphedema (10-40% volume difference) acquired as a
result of curative breast cancer surgery and were randomized to compression bandaging or garments within
the initial treatment phase of a DLT protocol. Primary endpoint was change in affected limb volume assessed
via volumetry, and secondary endpoints were symptom control and upper extremity function assessed via
visual analogue scales and the Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire,
respectively. Endpoints were assessed at day 10 of treatment and at 3 months and compared to baseline.
RESULTS:
Twenty-one subjects were available for analysis. The group receiving bandaging experienced greater median
volume reductions at 10 days (70 vs. 5 mL; p = 0.387) and at 3 months (97.5 vs. 50 mL; p = 0.182). The
bandaging group also experienced a greater increase in median DASH scores at 10 days (+20.9 vs. +5; p =
0.143) and at 3 months (+18.4 vs. +3.3; p = 0.065).
CONCLUSION:
Within the initial treatment phase of a DLT protocol for acquired, breast cancer-related lymphedema,
compression bandaging may lead to greater volume reduction but worse upper extremity functional status
(higher DASH scores) as compared to compression garments.
PMID: 21553314 [PubMed - as supplied by publisher]
Int Orthop. 2011 May 7. [Epub ahead of print]
Reinfection after two-stage revision for periprosthetic infection of total knee arthroplasty.
Kubista B, Hartzler RU, Wood CM, Osmon DR, Hanssen AD, Lewallen DG.
Source
Department of Orthopedic Surgery, Mayo Clinic, Rochester, MN, USA, Bernd.Kubista@meduniwien.ac.at.
Abstract
PURPOSE:
Limited data exist regarding the long-term results or risk factors for failure after two-stage reimplantation for
periprosthetic knee infection. The purpose of this retrospective review was to investigate infection-free
implant survival and identify variables associated with reinfection after this procedure. Furthermore, a staging
system was evaluated as a possible prognostic tool for patients undergoing two-stage reimplantation of
infected total knee arthroplasty (TKA).
METHODS:
In this level II, retrospective prognostic study, 368 patients with infected TKA treated with a two-stage
revision protocol at our institution between 1998 and 2006 were reviewed. Patients who developed
recurrent infection and an equal number of patients randomly selected for the control group were analysed
for risk factors associated with treatment failure.
RESULTS:
At the most recent follow-up, 58 (15.8%) patients had developed reinfection after the two-stage
reimplantation. The median time to reinfection was 1,303 days (3.6 years), with follow-up time ranging from
six to 2,853 days (7.8 years). The strongest positive predictors of treatment failure included chronic
lymphoedema [hazard ratio (HR) = 2.28, 95% confidence interval (CI) 1.16-4.48; p = 0.02),and revision
between resection and definitive reimplantation (HR = 2.13, 95% CI 1.20-3.79; p = 0.01, whereas patients
treated with intravenously administered Cefazolin had a significant reduction in recurrent infection rate (HR =
0.48, 95% CI 0.25-0.90; p = 0.02).
CONCLUSIONS:
Our findings should be of help in counselling patients regarding their prognosis when faced with two-stage
exchange for infected TKA and provide a basis for future comparisons.
PMID: 21553042 [PubMed - as supplied by publisher]
May 18, 2011
Proc (Bayl Univ Med Cent). 2011 Apr;24(2):81-5.
The sensitivity and specificity of sentinel lymph node biopsy for breast cancer at Baylor University Medical
Center at Dallas: a retrospective review of 488 cases.
Shiller SM, Weir R, Pippen J, Punar M, Savino D.
Source
Department of Pathology (Shiller, Weir, Punar, Savino) and Oncology (Pippen), Baylor University Medical
Center at Dallas and Baylor Charles A. Sammons Cancer Center at Dallas. Dr. Shiller is now at the Mayo
Clinic, Rochester, Minnesota.
Abstract
Sentinel lymph node (SLN) biopsy has become the standard of care for breast carcinoma management, as it
precludes the negative morbid effects-including decreased shoulder range of motion, lymphedema, and
paresthesias-of unnecessary axillary lymph node dissection. However, the method of pathologic evaluation
of the lymph node has been scrutinized to obtain the greatest sensitivity, specificity, and negative predictive
value, ultimately for the benefit of the patient. This retrospective study analyzed 488 biopsies completed by
two surgeons and read by multiple pathologists affiliated with Pathologists Biomedical Laboratories. When
metastatic disease was not grossly obvious, analysis of the SLN began with touch imprint cytology and, if
necessary, a frozen section analysis. On the subsequent day, three levels of the SLN were analyzed with
hematoxylin and eosin stain and immunohistochemistry with cytokeratin AE1-3 and the appropriate control.
Touch imprint cytology and/or frozen section analysis (where applicable) correctly identified 78 of 89
macrometastases, with a sensitivity of 88%, specificity of 100%, and negative predictive value of 97%.
Sensitivity was 72% for micrometastases and 60% for isolated tumor cells, each with 100% specificity. In
conclusion, the sensitivity and specificity of SLN biopsy at our institution compares with the higher end of
percentages reported in the literature.
PMID: 21566748 [PubMed - in process] PMCID: PMC3069509
Jpn J Clin Oncol. 2011 May 12. [Epub ahead of print]
Exogenous VEGF-C Augments the Efficacy of Therapeutic Lymphangiogenesis Induced by Allogenic Bone
Marrow Stromal Cells in a Rabbit Model of Limb Secondary Lymphedema.
Zhou H, Wang M, Hou C, Jin X, Wu X.
Source
Department of Vascular Surgery, Shandong Provincial Hospital, Shandong University, Jinan, Shandong
Province, China.
Abstract
OBJECTIVE:
To determine the effect of bone marrow stromal cells transplantation and vascular endothelial growth factor
C administration as a treatment for secondary lymphedema.
METHODS:
Bone marrow stromal cells and/or vascular endothelial growth factor C protein were injected into a rabbit
model of limb lymphedema. Water displacement volumetry was performed to measure limb volume changes.
Immunohistochemistry was performed to detect VEGFR-3 and to count lymph vessel. Western blot analysis
was performed to detect vascular endothelial growth factor C.
RESULTS:
Before treatment, rabbits had an average volume of edema in the limb of 61.25 ± 5.28, 62.37 ± 4.97,
60.58 ± 7.18 and 61.79 ± 4.33 ml (P = 0.753), respectively, in the BMSC + VEGF-C, bone marrow
stromal cell, vascular endothelial growth factor C and control groups. With therapy, this was reduced to an
average volume of 7.60 ± 3.02, 12.78 ± 3.41, 31.55 ± 3.51 and 62.33 ± 6.59 ml, respectively, in the four
groups 6 months after treatment. Quantitative analysis showed that the vessel numbers were significantly
increased in the BMSC + VEGF-C, bone marrow stromal cell and vascular endothelial growth factor C
groups compared with the control group at 28 days after the operation (P< 0.05). Western blot analysis
demonstrated that expression of vascular endothelial growth factor C was higher in the BMSC + VEGF-C
and BMSC groups.
CONCLUSIONS:
The combined treatment with bone marrow stromal cell transplantation and vascular endothelial growth
factor C administration is superior to bone marrow stromal cell transplantation alone in the treatment of limb
lymphedema. Bone marrow stromal cell transplantation and vascular endothelial growth factor C
administration could enhance the therapeutic effect of each other.
PMID: 21565926 [PubMed - as supplied by publisher]
Br J Dermatol. 2011 Feb 24. doi: 10.1111/j.1365-2133.2011.10275.x. [Epub ahead of print]
Severe lower limb cellulitis is best diagnosed by dermatologists and managed with shared care between
primary and secondary care.
Levell NJ, Wingfield CG, Garioch JJ.
Source
Dermatology Department, Norfolk and Norwich University Hospital, Norwich NR4 7UY, U.K.
Abstract
Summary Background Cellulitis is responsible for over 400 000 bed days per year in the English
National Health Service (NHS) at the cost of £96 million. Objectives An audit following transfer of care of
lower limb cellulitis managed in secondary care from general physicians to dermatologists. Methods
Review of patient details and work diaries from the first 40 months of implementation of the new model of
care. Results Of 635 patients referred with lower limb cellulitis 33% had other diagnoses which did not
require admission. Four hundred and seven of 425 patients with cellulitis were managed entirely as
outpatients, many at home. Twenty-eight per cent of patients with cellulitis had an underlying skin disease
identified and treated, which is likely to have reduced the risk of recurrent cellulitis, leg ulceration and
lymphoedema. Only 18 of 635 patients referred with lower limb cellulitis required hospital admission for
conventional treatment. Conclusions This new way of managing suspected lower limb cellulitis offered
substantial savings for the NHS, and benefits of early and accurate diagnosis with correct home treatment
for patients.
© 2011 The Authors. BJD © 2011 British Association of Dermatologists 2011.
PMID: 21564054 [PubMed - as supplied by publisher]
Cochrane Database Syst Rev. 2011 May 11;5:CD002224.
Primary groin irradiation versus primary groin surgery for early vulvar cancer.
van der Velden J, Fons G, Lawrie TA.
Source
Department of Obstetrics and Gynaecology, Academic Medical Centre, PO Box 22660, Meibergdreef 9,
Amsterdam, Netherlands, 1105 AZ.
Abstract
BACKGROUND:
Despite changes in technique, morbidity after surgery for vulvar cancer is high and mainly related to the groin
dissection. Primary radiotherapy to the groin is expected to result in lower morbidity. However, studies on
the efficacy of primary radiotherapy to the groin in terms of groin recurrences and survival show conflicting
results.
OBJECTIVES:
To determine whether the effectiveness and safety of primary radiotherapy to the inguinofemoral lymph
nodes in early vulvar cancer is comparable with surgery.
SEARCH STRATEGY:
We searched The Cochrane Gynaecological Cancer Group Specialised Register, Cochrane Central Register
of Controlled Trials (CENTRAL), MEDLINE and EMBASE from 1966 to July 2010.
SELECTION CRITERIA:
We selected randomised clinical trials (RCTs) comparing inguinofemoral lymph node dissection and primary
radiotherapy of the inguinofemoral lymph nodes for patients with early squamous cell cancer of the vulva.
DATA COLLECTION AND ANALYSIS:
Two reviewers independently assessed study quality and extracted results. Primary outcome measures were
the incidence of groin recurrences, patient survival and morbidity.
MAIN RESULTS:
No new RCTs were identified by the updated search. Out of twelve identified papers only one met the
selection criteria. From this one small RCT of 52 women, there was a trend towards increased groin
recurrence rates (relative risk (RR) 10.21, 95% confidence interval (CI) 0.59 to 175.78), lower disease-
specific survival rates (RR 3.70, 95% CI 0.87 to 15.80), less lymphoedema (RR 0.06, 95% CI 0.00 to
1.03) and fewer life-threatening cardiovascular complications (RR 0.08, 95% CI 0.00 to 1.45) in the
radiotherapy group. Primary surgery was associated with a longer hospital stay than primary groin irradiation
(RR 0.28, 95% CI 0.13 to 0.58).
AUTHORS' CONCLUSIONS:
Primary radiotherapy to the groin results in less morbidity but may be associated with a higher risk of groin
recurrence and decreased survival when compared with surgery. Due to the small numbers in this trial and
criticisms regarding the depth of radiotherapy applied, corroboration of these findings by larger RCTs using
a standardised radiotherapy method, is desirable. However, until better evidence is available, surgery should
be considered the first choice treatment for the groin nodes in women with vulvar cancer. Individual patients
not physically able to withstand surgery may be treated with primary radiotherapy.
PMID: 21563133 [PubMed - in process]
Breast Cancer Res Treat. 2011 May 12. [Epub ahead of print]
Does the effect of weight lifting on lymphedema following breast cancer differ by diagnostic method: results
from a randomized controlled trial.
Hayes SC, Speck RM, Reimet E, Stark A, Schmitz KH.
Source
Queensland University of Technology, School of Public Health, Institute of Biomedical Innovation, Brisbane,
Australia.
Abstract
The lymphedema diagnostic method used in descriptive or intervention studies may influence results found.
The purposes of this work were to compare baseline lymphedema prevalence in the physical activity and
lymphedema (PAL) trial cohort and to subsequently compare the effect of the weight-lifting intervention on
lymphedema, according to four standard diagnostic methods. The PAL trial was a randomized controlled
intervention study, involving 295 women who had previously been treated for breast cancer, and evaluated
the effect of 12 months of weight lifting on lymphedema status. Four diagnostic methods were used to
evaluate lymphedema outcomes: (i) interlimb volume difference through water displacement, (ii) interlimb size
difference through sum of arm circumferences, (iii) interlimb impedance ratio using bioimpedance
spectroscopy, and (iv) a validated self-report survey. Of the 295 women who participated in the PAL trial,
between 22 and 52% were considered to have lymphedema at baseline according to the four diagnostic
criteria used. No between-group differences were noted in the proportion of women who had a change in
interlimb volume, interlimb size, interlimb ratio, or survey score of ≥5, ≥5, ≥10%, and 1 unit, respectively
(cumulative incidence ratio at study end for each measure ranged between 0.6 and 0.8, with confidence
intervals spanning 1.0). The variation in proportions of women within the PAL trial considered to have
lymphoedema at baseline highlights the potential impact of the diagnostic criteria on population surveillance
regarding prevalence of this common morbidity of treatment. Importantly though, progressive weight lifting
was shown to be safe for women following breast cancer, even for those at risk or with lymphedema,
irrespective of the diagnostic criteria used.
PMID: 21562712 [PubMed - as supplied by publisher]
May 23, 2011
Ultrasound Obstet Gynecol. 2011 May 16. doi: 10.1002/uog.9048. [Epub ahead of print]
Experimental treatment of bilateral fetal chylothorax using in utero pleurodesis.
Yang YS, Ma GC, Shih JC, Chen CP, Chou CH, Yeh KT, Kuo SJ, Chen TH, Hwu WL, Lee TH, Chen
M.
Source
Department of Obstetrics and Gynecology, College of Medicine, and Hospital, National Taiwan University,
Taipei, Taiwan.
Abstract
OBJECTIVE:
The use and efficacy of in utero pleurodesis for experimental treatment of bilateral fetal chylothorax (FC)
were assessed.
METHODS:
A total of 78 fetuses with bilateral pleural effusion referred to three tertiary referral centers in Taiwan
between 2005 and 2009 were analyzed for the karyotype (by amniocentesis) and the lymphocyte ratio in
pleural effusion (by thoracocentesis). Of these, 49 (62.8%) fetuses with a normal karyotype were
recognized to be FC; in which, 45 accepted intrapleural injection with 0.1KE OK-432 per side per
treatment. The clinical (e.g. hydrops vs. no hydrops) and genetic (e.g. mutations in the reported
lymphedema-associated loci: VEGFR3, PTPN11, FOXC2, ITGA9) parameters, as well as outcomes of
the treatment were evaluated. Survival at 1 year of age was defined as long-term survival (LSR) in this study.
RESULTS:
The overall LSR was 35.6% (16/45). The LSR in non-hydropic and hydropic fetuses were 66.7% (12/18)
and 14.8% (4/27), respectively. The LSR further decreased to 29.4% (10/34) if we only included those
onset at second trimester and excluded those onset at third trimester. Notably, 29.6% (8/27) of hydropic
fetuses was found to have mutations in the four loci we examined.
CONCLUSION:
In non-hydropic FC cases, the OK-432 pleurodesis appeared to be an experimental alternative to the gold-
standard thoracoamniotic shunting in hospitals where such treatment is not available due to technical and
logistic reasons but in hydropic fetuses the proposed treatment is ineffective (15% survival versus 44-66%
with shunting according to previous reports). Copyright © 2011 ISUOG. Published by John Wiley & Sons,
Ltd.
Copyright © 2011 ISUOG. Published by John Wiley & Sons, Ltd.
PMID: 21584887 [PubMed - as supplied by publisher]
Lab Invest. 2011 May 16. [Epub ahead of print]
Role of COX-2 in lymphangiogenesis and restoration of lymphatic flow in secondary lymphedema.
Kashiwagi S, Hosono K, Suzuki T, Takeda A, Uchinuma E, Majima M.
Source
1] Department of Pharmacology, Kitasato University School of Medicine, Kanagawa, Japan [2]
Department of Plastic and Aesthetic Surgery, Kitasato University School of Medicine, Kanagawa, Japan.
Abstract
The pathophysiology of secondary lymphedema remains poorly understood. To clarify the roles of
cyclooxygenase (COX)-2 in enhancement of lymphangiogenesis during secondary lymphedema, we tested a
mouse tail model and evaluated the recurrence of lymph flow. To induce lymphedema, a circumferential
incision was made in the tail of anesthetized mice to sever the dermal lymphatic vessels. The maximum
diameters of the tails were measured weekly. We found that the diameters of the tails around the wounds
were markedly increased after surgery, and reached maximum size 2 weeks after wounding in mice without
a COX-2 inhibitor, celecoxib (Celecoxib-). Expression of COX-2 in wound granulation tissues was
markedly increased 1 week after surgery compared with unwounded naive control mice. In Celecoxib-,
recurrence of lymphatic flow in the wound granulation tissues was detected 3 weeks after surgical treatment.
In contrast, lymphatic flow was markedly suppressed in mice treated with celecoxib (Celecoxib+). Newly
formed lymphatic structures were identified in the granulation tissues formed at wounded lesions in
Celecoxib-, whereas those were markedly suppressed in Celecoxib+. Interstitial tissue pressures in the distal
areas of the tail wounds were markedly increased in Celecoxib+ with reduced expression of vascular
endothelial cell growth factor (VEGF)-C. F4/80-positive cells were accumulated to the wound granulation
tissues in Celecoxib-, and the accumulation of these cells was suppressed in Celecoxib+. Prostaglandin E(2)
(PGE(2)) upregulated the expressions of VEGF-A and VEGF-C in cultured macrophages, but not human
lymphatic microvascular endothelial cells. The present study therefore suggests that lymphangiogenesis,
together with recurrence of lymph flow after surgical induction of lymphedema, is upregulated by COX-2
possibly via generation of PGs.Laboratory Investigation advance online publication, 16 May 2011; doi:
10.1038/labinvest.2011.84.
PMID: 21577211 [PubMed - as supplied by publisher]
Phlebology. 2011 May 16. [Epub ahead of print]
Evaluation of lymph drainage using bioelectrical impedance of the body.
de Godoy JM, Valente FM, Azoubel LM, Godoy MF.
Source
* Department of Cardiology and Cardiovascular Surgery, Medicine School of São José do Rio Preto-
FAMERP, Research CNPq (National Council for Research and Development), Brazil.
Abstract
AIM:
The aim of this study was to investigate the effects of manual and mechanical lymph drainage on the
bioelectrical composition of body tissues of patients with lymphoedema of the lower limbs.
METHOD:
Twenty-one patients with lymphoedema of one leg were evaluated using single frequency bioelectrical
impedance with four electrodes (SF-BIA4) immediately before and after a combination of manual and
mechanical lymph drainage. Statistical analysis used the two-tailed paired t-test with an alpha error of 5%
being considered acceptable.
RESULTS:
On comparing the results before and after lymph drainage, statistically significant differences were identified
for both lymphoedematous and apparently healthy legs, but there were no significant differences in the
alterations caused by the treatment between the healthy and lymphoedematous limbs of the same patient.
CONCLUSION:
It was concluded that the association of manual and mechanical lymph drainage both modified the body
composition as identified by bioelectrical impedance, and reduced the oedema.
PMID: 21576705 [PubMed - as supplied by publisher]
J Cell Biol. 2011 May 16;193(4):607-18.
Lymphatic vascular morphogenesis in development, physiology, and disease.
Schulte-Merker S, Sabine A, Petrova TV.
Source
Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences, and University Medical Centre, 3584
CT Utrecht, Netherlands.
Abstract
The lymphatic vasculature constitutes a highly specialized part of the vascular system that is essential for the
maintenance of interstitial fluid balance, uptake of dietary fat, and immune response. Recently, there has
been an increased awareness of the importance of lymphatic vessels in many common pathological
conditions, such as tumor cell dissemination and chronic inflammation. Studies of embryonic development
and genetically engineered animal models coupled with the discovery of mutations underlying human
lymphedema syndromes have contributed to our understanding of mechanisms regulating normal and
pathological lymphatic morphogenesis. It is now crucial to use this knowledge for the development of novel
therapies for human diseases.
PMID: 21576390 [PubMed - in process]
Dermatol Surg. 2011 May 16. doi: 10.1111/j.1524-4725.2011.02002.x. [Epub ahead of print]
Prospective, Randomized, Controlled Trial Comparing a New Two-Component Compression System with
Inelastic Multicomponent Compression Bandages in the Treatment of Leg Lymphedema.
Lamprou DA, Damstra RJ, Partsch H.
Source
Department of Dermatology, Phlebology, and Lymphology, Nij Smellinghe Hospital, Drachten, The
Netherlands Private Practice, Vienna, Austria.
Abstract
BACKGROUND New, less-bulky, short-stretch compression bandages could be a valuable alternative in
the management of lymphedema of the leg. OBJECTIVE To compare the effectiveness of a two-component
compression (2CC) system in the treatment of leg lymphedema with that of the traditional treatment with
conventional inelastic multicomponent compression bandages (IMC). METHODS Thirty hospitalized
patients with moderate to severe unilateral lymphedema (stage II-III) of the leg were included. Patients were
divided in two groups; one (n=15) received a 2CC, and the other (n=15) received IMC. Primary outcome
was volume reduction of the affected leg; secondary outcome was loss of interface pressure. RESULTS
Median leg volumes before bandaging were 4,150 mL (2CC) and 4,360 mL (IMC). Median volume
reduction after 2 hours was 120 mL (2.9%) with the 2CC system and 80 mL (1.8%) with IMC (p>.
05). After 24 hours, volume reduction was 8.4% and 4.4% respectively (p>.05). Interface pressure
dropped significantly within 2 hours of bandage application in both groups. CONCLUSION Our results
indicate that the 2CC system forms a suitable alternative to IMC in the conventional treatment of moderate
to severe lymphedema. This study was supported by a 3M Health Care grant to a foundation.
© 2011 by the American Society for Dermatologic Surgery, Inc.
PMID: 21575097 [PubMed - as supplied by publisher
J Am Acad Dermatol. 2011 Jun;64(6):1223-4.
Hidradenitis suppurativa complicated by severe lymphedema and lymphangiectasias.
Moosbrugger EA, Mutasim DF.
Source
Department of Dermatology, University of Cincinnati College of Medicine, Cincinnati, Ohio.
PMID: 21571207 [PubMed - in process]
Phlebology. 2011 May 16. [Epub ahead of print]
Evaluation of lymph drainage using bioelectrical impedance of the body.
de Godoy JM, Valente FM, Azoubel LM, Godoy MF.
Source
* Department of Cardiology and Cardiovascular Surgery, Medicine School of São José do Rio Preto-
FAMERP, Research CNPq (National Council for Research and Development), Brazil.
Abstract
AIM:
The aim of this study was to investigate the effects of manual and mechanical lymph drainage on the
bioelectrical composition of body tissues of patients with lymphoedema of the lower limbs.
METHOD:
Twenty-one patients with lymphoedema of one leg were evaluated using single frequency bioelectrical
impedance with four electrodes (SF-BIA4) immediately before and after a combination of manual and
mechanical lymph drainage. Statistical analysis used the two-tailed paired t-test with an alpha error of 5%
being considered acceptable.
RESULTS:
On comparing the results before and after lymph drainage, statistically significant differences were identified
for both lymphoedematous and apparently healthy legs, but there were no significant differences in the
alterations caused by the treatment between the healthy and lymphoedematous limbs of the same patient.
CONCLUSION:
It was concluded that the association of manual and mechanical lymph drainage both modified the body
composition as identified by bioelectrical impedance, and reduced the oedema.
PMID: 21576705 [PubMed - as supplied by publisher]
May 26, 2011
Clin Genet. 2011 May 19. doi: 10.1111/j.1399-0004.2011.01706.x. [Epub ahead of print]
Massively parallel sequencing and identification of genes for primary lymphoedema: a perfect fit.
Ostergaard P, Simpson M, Jeffery S.
Source
Medical Genetics Unit, Biomedical Sciences, St George's University of London, London, UK Division of
Genetics and Molecular Medicine, King's College London School of Medicine, Guy's Hospital, London,
UK.
Abstract
Ostergaard P, Simpson MA, Jeffery S. Massively parallel sequencing and the identification of genes for
primary lymphoedema: a perfect fit. Primary lymphoedema is a clinically and genetically heterogeneous
group of disorders characterized by disruption of the lymphatic system. To date, the majority of the
causative genes in primary lymphoedema have been identified through linkage analysis in large families with
multiple affected subjects. Studies aimed at isolating additional genes responsible for primary lymphoedema
have been hampered by cohorts comprised primarily of sporadic cases and small affected kindreds. In the
absence of genetic heterogeneity, recent development of massively parallel DNA sequencing technology,
specifically exome sequencing, has provided novel paradigms for disease gene identification in such cohorts.
In this review, we summarize the novel approaches to disease gene discovery with massively parallel
sequencing also known as Next Generation Sequencing (NGS), and show how the selection of unrelated
affected cases from clinically homogenous phenotypic subclassifications is proving to be a successful
approach for disease gene discovery in primary lymphoedema.
© 2011 John Wiley & Sons A/S.
PMID: 21595654 [PubMed - as supplied by publisher