JOURNAL OF CUTANEOUS PATHOLOGY, Issue 7 2006
Pratistadevi K. Ramdial
Background:, Advanced Kaposi's sarcoma is frequently associated with chronic lymphedema (cLO). The histopathological features of lymphedematous HIV-associated KS (KS) are poorly documented and the co-existence of fibroma-like nodules in lymphedematous KS is under-recognized. The aims of this study were to assess the clinicopathological spectrum and diagnostic difficulties associated with lymphedematous KS and to highlight the clinicopathological profile of fibroma-like nodules. In addition, the pathogenesis of fibroma-like nodules and cLO is revisited. Materials and methods:, Prospective 17-month clinicopathological study of all biopsies from patients with lymphedematous KS. Results:, Seventy-four biopsies, the majority from the lower limbs, from 41 patients were evaluated. Nineteen, 14, five and three patients had one, two, three or four biopsies each, respectively. In 14 biopsies, there was poor clinicopathological correlation of KS stage. Exclusive lesional KS (patch, plaque, nodule or lymphangioma-like) was identified in 29 biopsies; 23 and eight biopsies demonstrated KS or fibroma-like morphology and the adjacent dermis demonstrated cLO. There was variable intratumoral and peritumoral venous compression and lymphatic dilatation. Fourteen biopsies demonstrated cLO exclusively. Smaller fibroma-like nodules lacked KS spindle cells, whereas >5 mm nodules demonstrated focal KS spindle cell proliferation and aggregation on extensive sectioning. The subcutis of 42 biopsies demonstrated variable fibrosis, hemosiderin deposits, lymphocytes, plasma cells, KS, interstitial granular material and pools of lymph fluid. Subcutaneous abscesses were identified in six biopsies. All biopsies had variable epidermal features of cLO. Conclusions:, cLO influences clinicopathological correlation of KS stage and may also mask the presence of KS and the co-existence of subcutaneous abscesses. Smaller fibroma-like nodules are hypothesized to be a manifestation of cLO that have the potential to acquire the characteristics of KS. Lymphatic and venous obstruction, protein-rich interstitial fluid, tissue hemosiderin and subcutaneous infection are hypothesized to play a combined role in the evolution and perpetuation of cLO. [source]

Expression of vascular endothelial growth factor-C correlates with the lymphatic microvessel density and the nodal status in oral squamous cell cancer

JOURNAL OF ORAL PATHOLOGY & MEDICINE, Issue 8 2003
Roland Sedivy
Abstract Background:, The cause of preferential metastatic spreading to cervical lymph nodes in oral squamous cell cancer (SCC) is not quite clear. As the density of microvessels may influence the metastatic behaviour, we were interested in how the density of blood/lymphatic microvessels are related to primary SCC and the clinical course of the disease. Methods:, Lymphatic and blood microvessels of 28 patients with oral SCC were identified immunohistochemically by antibodies against podoplanin and CD34, respectively. Lymphatic microvessel density (LVD) and blood microvessel density (MVD), and the expression of VEGF-C were determined. These findings were compared with the long-term clinicopathological data of the patients. Results:, LVD and MVD were significantly higher than in control tissues. The amount of lymphatic microvessels correlated positively with the expression of VEGF-C, the tumour grade, the nodal status and with later appearing metastasis. The latter three parameters, however, did not influence the clinical course of the disease. Conclusions:, VEGF-C expression in oral SCC triggers lymphatic angiogenesis, which may result in a higher risk for cervical lymph node metastasis. The angiogenetic effect of VEGF-C may also favour the onset of late lymphatic and haematogenous metastases. [source]

Lymphatics at the crossroads of angiogenesis and lymphangiogenesis

JOURNAL OF ANATOMY, Issue 6 2004
Claudio Scavelli
Abstract The lymphatic system is implicated in interstitial fluid balance regulation, immune cell trafficking, oedema and cancer metastasis. However, the sequence of events that initiate and coordinate lymphatic vessel development (lymphangiogenesis) remains obscure. In effect, the understanding of physiological regulation of lymphatic vasculature has been overshadowed by the greater emphasis focused on angiogenesis, and delayed by a lack of specific markers, thereby limiting this field to no more than a descriptive characterization. Recently, new insights into lymphangiogenesis research have been due to the discovery of lymphatic-specific markers and growth factors of vascular endothelial growth factor (VEGF) family, such as VEGF-C and VEGF-D. Studies using transgenic mice overexpressing VEGF-C and VEGF-D have demonstrated a crucial role for these factors in tumour lymphangiogenesis. Knowledge of lymphatic development has now been redefined at the molecular level, providing an interesting target for innovative therapies. This review highlights the recent insights and advances into the field of lymphatic vascular research, outlining the most important aspects of the embryo development, structure, specific markers and methods applied for studying lymphangiogenesis. Finally, molecular mechanisms involved in the regulation of lymphangiogenesis are described. [source]

Recanalization of the Collecting Lymphatics in Rabbit Hind Leg

MICROCIRCULATION, Issue 5 2006
FUMITAKA IKOMI
ABSTRACT Objective: This study was designed to examine whether mature collecting lymphatics can regenerate in the adult tissue or not. Materials and Methods: The X-ray lymphograms were used to detect network of the collecting lymphatics in rabbit hind leg. Regeneration of the lymphatics was observed after surgical removal of the popliteal lymph node or a part of the popliteal afferent lymphatic. Structure and mechanical properties of the lymphatics were also examined by light and electron microscopes and in vitro functional experiments. Results: One week after removal of the lymph node, only an afferent lymphatic and a deposit of the contrast medium at the popliteal region were observed. Four weeks after the removal, the connection of the afferent and efferent lymphatics at the popliteal region, and collateral lymphatics were present in the leg. Further, 4 weeks after 1-mm excisions of a part of the lymphatic, recanalization was observed between the central and peripheral cut ends of the lymphatic but not after 3- and 10-mm excisions. Endothelial cells and smooth muscle cells could be observed by electron microscope, and contractile proteins, and alpha-smooth muscle actin SM1 and SM2 were immunofluorescently detected in both intact and the regenerated lymphatic walls. In both lymphatics, norepinephrine and acetylcholine induced dose-dependent constriction and dilation of the vessels, respectively. Conclusion: The present study demonstrated that mature collecting lymphatics are able to regenerate in the adult tissues. [source]

Regional Variations of Contractile Activity in Isolated Rat Lymphatics

MICROCIRCULATION, Issue 6 2004
ANATOLIY A. GASHEV
ABSTRACT Objective: To evaluate lymphatic contractile activity in different regions of the lymphatic system in a single animal model (the rat thoracic duct, mesenteric, cervical, and femoral lymphatics) in response to changes in lymph pressure and flow. Methods: The systolic and diastolic diameters of isolated, cannulated, and pressurized lymphatic vessels were measured. Contraction frequency, ejection fraction, and fractional pump flow were determined. The influences of incrementally increased transmural pressure (from 1 to 9 cm H2O) and imposed flow (from 1 to 5 cm H2O transaxial pressure gradient) were investigated. Results: The authors determined regional differences in lymphatic contractility in response to pressure and imposed flow. They found the highest pumping (at the optimal pressure levels) in mesenteric lymphatics and lowest pumping in thoracic duct. All lymphatics had their optimal pumping conditions at low levels of transmural pressure. Different degrees of the flow-induced inhibition of the pump were observed in the different types of lymphatics. During high flow, the active lymph pumps in thoracic duct and cervical lymphatics were almost completely abolished, whereas mesenteric and femoral lymphatics still exhibited significant active pumping. Conclusions: The active lymph pumps in different regions of the rat body express variable relative strengths and sensitivities that are predetermined by different hydrodynamic factors and regional outflow resistances in their respective locations. [source]

Predictive factors for esophageal stenosis after endoscopic submucosal dissection for superficial esophageal cancer

DISEASES OF THE ESOPHAGUS, Issue 7 2009
H. Mizuta
SUMMARY Endoscopic submucosal dissection (ESD) has been utilized as an alternative treatment to endoscopic mucosal resection for superficial esophageal cancer. We aimed to evaluate the complications associated with esophageal ESD and elucidate predictive factors for post-ESD stenosis. The study enrolled a total of 42 lesions of superficial esophageal cancer in 33 consecutive patients who underwent ESD in our department. We retrospectively reviewed ESD-associated complications and comparatively analyzed regional and technical factors between cases with and without post-ESD stenosis. The regional factors included location, endoscopic appearance, longitudinal and circumferential tumor sizes, depth of invasion, and lymphatic and vessel invasion. The technical factors included longitudinal and circumferential sizes of mucosal defects, muscle disclosure and cleavage, perforation, and en bloc resection. Esophageal stenosis was defined when a standard endoscope (9.8 mm in diameter) failed to pass through the stenosis. The results showed no cases of delayed bleeding, three cases of insidious perforation (7.1%), two cases of endoscopically confirmed perforation followed by mediastinitis (4.8%), and seven cases of esophageal stenosis (16.7%). Monovalent analysis indicated that the longitudinal and circumferential sizes of the tumor and mucosal defect were significant predictive factors for post-ESD stenosis (P < 0.005). Receiver operating characteristic analysis showed the highest sensitivity and specificity for a circumferential mucosal defect size of more than 71% (100 and 97.1%, respectively), followed by a circumferential tumor size of more than 59% (85.7 and 97.1%, respectively). It is of note that the success rate of en bloc resection was 95.2%, and balloon dilatation was effective for clinical symptoms in all seven patients with post-ESD stenosis. In conclusion, the most frequent complication with ESD was esophageal stenosis, for which the sizes of the tumor and mucosal defect were significant predictive factors. Although ESD enables large en bloc resection of esophageal cancer, practically, in cases with a lesion more than half of the circumference, great care must be taken because of the high risk of post-ESD stenosis. [source]

Anti-VEGF-A therapy reduces lymphatic vessel density and expression of VEGFR-3 in an orthotopic breast tumor model

INTERNATIONAL JOURNAL OF CANCER, Issue 10 2007
Brandt Whitehurst
Abstract Because metastasis contributes significantly to cancer mortality, understanding its mechanisms is crucial to developing effective therapy. Metastasis is facilitated by lymphangiogenesis, the growth of new intratumoral or peritumoral lymphatic vessels from pre-existing vessels. Vascular endothelial growth factor A (VEGF-A) is a well-known angiogenic factor. Increasing evidence implicates VEGF-A in lymphangiogenesis, although the mechanism of its pro-lymphangiogenic effect is poorly understood. We examined the effect of the anti-VEGF-A neutralizing antibody 2C3 on tumor lymphangiogenesis and metastasis in an orthotopic breast carcinoma model using MDA-MB-231 cells and its luciferase-tagged derivative, 231-Luc+ cells. Anti-VEGF-A antibody therapy reduced blood and lymphatic vessel densities by 70% and 80%, respectively, compared with the control antibody. Treatment with 2C3 antibody also decreased incidence of lymphatic and pulmonary metastases by 3.2- and 4.5-fold, respectively. Macrophage infiltration was reduced in 2C3-treated tumors by 32%, but VEGF-C expression was unchanged. In contrast, neoplastic cells and blood vessels in tumors from 2C3-treated mice expressed significantly less angiopoietin-2 (Ang-2) than tumors from control mice. The reduction in Ang-2 was associated with inhibition of VEGFR-3 expression in intratumoral lymphatic endothelial cells. Both VEGF-A and Ang-2 upregulated the expression of VEGFR-3 in cultured lymphatic endothelial cells. VEGF-A induced proliferation of lymphatic endothelial cells was reduced by 50% by soluble Tie-2, suggesting that Ang-2 is an intermediary of the pro-lymphangiogenic VEGF-A effect. These results suggest a novel mechanism by which anti-VEGF-A therapy may suppress tumor lymphangiogenesis and subsequent metastasis supporting the use of anti-VEGF-A therapy to control metastasis clinically. © 2007 Wiley-Liss, Inc. [source]

The distribution of skeletal lesions in treponemal disease: is the lymphatic system responsible?

INTERNATIONAL JOURNAL OF OSTEOARCHAEOLOGY, Issue 3 2002
Hallie R. Buckley
Abstract The differential diagnosis of bone lesions in treponemal disease is well established in palaeopathology. However, the actual mechanism responsible for the characteristic distribution of bone involvement is not as clear. Two mechanisms are proposed in the literature. Firstly, that bone lesions are the result of direct extension from the skin rash of the secondary stage of disease. Secondly, that bones situated closer to the skin are more vulnerable to local trauma and therefore more likely to elicit a subperiosteal bone response. We propose an alternative explanation for the characteristic distribution of bone lesions in treponemal disease. This explanation is based on the close association between the lymphatic and skeletal systems and the pathogenesis of treponemal disease. This paper argues that the position of the lymphatic nodes and vessels, with little soft tissue intervention between bone tissue, mirrors the characteristic pattern of skeletal involvement in treponemal disease. Copyright © 2002 John Wiley & Sons, Ltd. [source]

Expression of vascular endothelial growth factor-C correlates with the lymphatic microvessel density and the nodal status in oral squamous cell cancer

A rational approach to internal mammary node biopsy in the era of lymphatic mapping for breast cancer

JOURNAL OF SURGICAL ONCOLOGY, Issue 1 2002
Kenneth A. Kern MD
First page of article [source]

Recanalization of the Collecting Lymphatics in Rabbit Hind Leg

Establishment of Rat Lymphatic Endothelial Cell Line

MICROCIRCULATION, Issue 2 2003
Risuke Mizuno
ABSTRACT Objective: The objective of the present study was to establish a rat lymphatic endothelial cell line and then to investigate the morphological and immunohistochemical properties of the cells. Methods: The lymphatic endothelial cells of rat thoracic ducts were isolated enzymatically by trypsin digestion and were cultured in endothelium growth medium (EGM)-2 in an atmosphere of low oxygen (5% O2, 5% CO2, and 90% N2) or high oxygen (21% O2, 5% CO2, and 74% N2). Results: The number of the cells cultured in the low-oxygen atmosphere was significantly larger than that obtained in the high-oxygen atmosphere. The cultured cells in the low-oxygen atmosphere showed a monolayer with uniform cobblestone appearance, suggesting the morphological properties of endothelial cells. Factor VIII-related antigen and cell surface carbohydrates (i.e., D-galactose , and D- N -acetylgalactosamine ,) were found on the lymphatic cultured cells. The phagocytosis of 1,1-diocadecyl1-3,3,3,,3,-tetramethylindocarbocyanine perchlorate-labeled acetylated low-density lipoprotein also was observed in the cultured cells. The cytoskeleton protein F-actin was located on the plasma membrane of the cultured cells as circumferential thin bundles and in the cytoplasma as filamentous bundles. Conclusions: The present study indicates that the choice of EGM-2 as a culture medium and the hypoxic atmosphere (,5%) enabled us to establish rat lymphatic endothelial cell line. [source]

Development of the avian lymphatic system,

MICROSCOPY RESEARCH AND TECHNIQUE, Issue 2 2001
Jörg Wilting
Abstract Recently, highly specific markers of the lymphatic endothelium have been found enabling us to reinvestigate the embryonic origin of the lymphatics. Here we present a review of our studies on the development of the lymphatic system in chick and quail embryos. We show that the lymphatic endothelium is derived from two sources: the embryonic lymph sacs and mesenchymal lymphangioblasts. Proliferation studies reveal a BrdU-labeling index of 11.5% of lymph sac endothelial cells by day 6.25, which drops to 3.5% by day 7. Lymphangioblasts are able to integrate into the lining of lymph sacs. Lymphatic endothelial cells express the vascular endothelial growth factor (VEGF) receptors-2 and -3. Their ligand, VEGF-C, is expressed almost ubiquitously in embryonic and fetal tissues. Elevated expression levels are found in the tunica media of large blood vessels, which usually serve as major routes for growing lymphatics. The homeobox gene, Prox1, is expressed in lymphatic but not in blood vascular endothelial cells throughout all stages examined, namely, in developing lymph sacs of day 6 embryos and in lymphatics at day 16. Experimental studies show the existence of lymphangioblasts in the mesoderm, a considerable time before the development of the lymph sacs. Lymphangioblasts migrate from the somites into the somatopleure and contribute to the lymphatics of the limbs. Our studies indicate that these lymphangioblasts already express Prox1. Microsc. Res. Tech. 55:81,91, 2001. © 2001 Wiley-Liss, Inc. [source]

Molecular markers of circulating melanoma cells

PIGMENT CELL & MELANOMA RESEARCH, Issue 2 2007
Sandra Medic
Summary Of all skin cancers, cutaneous malignant melanoma (CMM) is the most aggressive and the life expectancy of patients with lymphatic or systemic metastases is dramatically reduced. Understandably therefore, scientists and clinicians have focused on improving diagnostic and prognostic techniques. Of these, perhaps the most promising are multimarker real-time RT-PCR and microarray for detection of circulating CMM cells in peripheral blood. While the optimal set of markers is still to be identified that can accurately assess disease severity and progression at all clinical stages of the disease, recent progress has been dramatic. Here we provide an exhaustive review of recent studies in which a variety of markers are assessed. Moreover, the efficacy of the markers relative to clinical stage is discussed in light of experimental findings. From these studies, it is apparent that researchers are now much closer to defining a set of markers of circulating cells that can be utilized in routine diagnostic tests. [source]

A cohort mortality study of chemical laboratory workers at Department of Energy Nuclear Plants,

AMERICAN JOURNAL OF INDUSTRIAL MEDICINE, Issue 9 2008
Travis Kubale PhD
Abstract Objective This study evaluates the mortality experience of 6,157 chemical laboratory workers employed at United States Department of Energy facilities. Methods All cause, all cancer and cause-specific standardized mortality ratios were calculated. Cox regression analyses were conducted to further evaluate the relation between chemical exposure and mortality risk due to selected cancers. Results The mortality due to all causes combined and all cancers combined were below expectation for the cohort. There were no statistically significant elevations reported among males for any specific cancer or non-cancer outcome. There no statistically significant elevations among females for any specific non-cancer and most specific cancers; however, multiple myeloma deaths were significantly elevated (SMR,=,3.56; 95% CI,=,1.43,7.33; number of observed deaths, n,=,7). Statistically significant elevations were seen among workers employed 20+ years for leukemia using both 2- and 5-year lag periods. Also, a statistically significant positive trend of elevated lung cancer mortality with increasing employment duration was seen using both 5- and 10-year lags. A similar trend was seen for smoking related cancers among men. Conclusion While lymphatic and hematopoietic cancer mortality was below expectation, a significant elevation of multiple myeloma deaths among females and an elevation of leukemia among workers employed 20+ years (possibly due to radiation and benzene exposure) were observed. A NIOSH case,control study is underway to examine more closely the relation between multiple myeloma and a variety of chemical exposures among workers employed at the Oak Ridge K-25 facility. Am. J. Ind. Med. 51:656,667, 2008. Published 2008 Wiley-Liss, Inc. [source]

Lymphatic/Blood Endothelial Cell Connections at the Capillary Level in Adult Rat Mesentery

THE ANATOMICAL RECORD : ADVANCES IN INTEGRATIVE ANATOMY AND EVOLUTIONARY BIOLOGY, Issue 10 2010
Jennifer L. Robichaux
Abstract Analyses of microvascular networks with traditional tracer filling techniques suggest that the blood and lymphatic systems are distinct without direct communications, yet involvement of common growth factors during angiogenesis and lymphangiogenesis suggest that interactions at the capillary level are possible. To investigate the structural basis for lymphatic/blood endothelial cell connections during normal physiological growth, the objective of this study was to characterize the spatial relations between lymphatic and blood capillaries in adult rat mesenteric tissue. Using immunohistochemical methods, adult male Wistar rat mesenteric tissues were labeled with antibodies against PECAM (an endothelial marker) and LYVE-1, Prox-1, or Podoplanin (lymphatic endothelial markers) or NG2 (a pericyte marker). Positive PECAM labeling identified apparent lymphatic/blood endothelial cell connections at the capillary level characterized by direct contact or direct alignment with one another. In PECAM labeled networks, a subset of the lymphatic and blood capillary blind ends were connected with each other. Intravital imaging of FITC-Albumin injected through the femoral vein did not identify lymphatic vessels. At contact sites, lymphatic endothelial markers did not extend along blood capillary segments. However, PECAM positive lymphatic sprouts, structurally similar to blood capillary sprouts, lacked observable lymphatic marker labeling. These observations suggest that nonlumenal lymphatic/blood endothelial cell interactions exist in unstimulated adult microvascular networks and highlight the potential for lymphatic/blood endothelial cell plasticity. Anat Rec 293:1629,1638, 2010. © 2010 Wiley-Liss, Inc. [source]

Tubular Carcinoma of the Breast: A Population-Based Study of Nodal Metastases at Presentation and of Patterns of Relapse

THE BREAST JOURNAL, Issue 1 2001
H. A. Kader MD
Abstract: Tubular carcinoma of the breast (TCB) is a recognized histologic variant of infiltrating ductal carcinoma (IDC) and has been considered to have a comparatively favorable prognosis. However, previous studies have been based on small numbers of cases, some pure TCB and some mixed histology, or have not employed an appropriate comparison group. In this study 171 pure TCB cases and a comparison group of 386 cases with grade I (well differentiated) IDC were identified in a population-based database maintained by the British Columbia Cancer Agency (BCCA). The proportion of cases with axillary nodal involvement at presentation was lower in TCB cases than in the grade I IDC comparison group (12.9% and 23.9%, respectively; p < 0.05). Low-risk tumors (T1 and without vascular lymphatic or perineural invasion) were more prevalent in the TCB patients than in the grade I IDC patients (66.7% and 60.0%; p < 0.05). Low-risk TCB cases had a significantly lower rate of nodal metastases at presentation than low-risk grade I IDC cases (7.0% and 13.2%; p < 0.05). Kaplan,Meier and log-rank analyses indicated a statistically significantly lower rate of local recurrence in TCB cases than among IDC cases (p < 0.05) and a trend toward a lower rate of systemic relapse in TCB cases (p = 0.07). However, no difference in disease-specific survival was observed between TCB cases and grade I IDC comparisons. We conclude that the biologic behavior of TCB was more favorable than that of a comparison group of IDC cases. In view of the low incidence of axillary node metastases at presentation in the low-risk TCB subset (7%), axillary dissection may be omitted as part of the initial surgical management in these patients. [source]

Candidate's Thesis: The Application of Sentinel Node Radiolocalization to Solid Tumors of the Head and Neck: A 10-Year Experience,

THE LARYNGOSCOPE, Issue 1 2004
James C. Alex MD
Abstract Objectives/Hypothesis The goals of the research study were to develop an easily mastered, accurate, minimally invasive technique of sentinel node radiolocalization with biopsy (SNRLB) in the feline model; to compare it with blue-dye mapping techniques; and to test the applicability of sentinel node radiolocalization biopsy in three head and neck tumor types: N0 malignant melanoma, N0 Merkel cell carcinoma, and N0 squamous cell carcinoma. Study Design Prospective consecutive series studies were performed in the feline model and in three head and neck tumor types: N0 malignant melanoma (43 patients), N0 Merkel cell carcinoma (8 patients), and N0 squamous cell carcinoma (20 patients). Methods The technique of sentinel node radiolocalization with biopsy was analyzed in eight felines and compared with blue-dye mapping. Patterns of sentinel node gamma emissions were recorded. Localization success rates were determined for blue dye and sentinel node with radiolocalization biopsy. In the human studies, all patients had sentinel node radiolocalization biopsy performed in a similar manner. On the morning of surgery, each patient had sentinel node radiolocalization biopsy of the sentinel lymph node performed using an intradermal or peritumoral injection of technetium Tc 99m sulfur colloid. Sentinel nodes were localized on the skin surface using a handheld gamma detector. Gamma count measurements were obtained for the following: 1) the "hot" spot/node in vivo before incision, 2) the hot spot/node in vivo during dissection, 3) the hot spot/node ex vivo, 4) the lymphatic bed after hot spot/node removal, and 5) the background in the operating room. The first draining lymph node(s) was identified, and biopsy of the node was performed. The radioactive sentinel lymph node(s) was submitted separately for routine histopathological evaluation. Preoperative lymphoscintigrams were performed in patients with melanoma and patients with Merkel cell carcinoma. In patients with head and neck squamous cell carcinoma, the relationship between the sentinel node and the remaining lymphatic basin was studied and all patients received complete neck dissections. The accuracy of sentinel node radiolocalization with biopsy, the micrometastatic rate, the false-negative rate, and long-term recurrence rates were reported for each of the head and neck tumor types. In the melanoma study, the success of sentinel node localization was compared for sentinel node radiolocalization biopsy, blue-dye mapping, and lymphoscintigraphy. In the Merkel cell carcinoma study, localization rates were evaluated for sentinel node radiolocalization biopsy and lymphoscintigraphy. In the head and neck squamous cell carcinoma study, the localization rate of sentinel node radiolocalization biopsy and the predictive value of the sentinel node relative to the remaining lymphatic bed were determined. All results were analyzed statistically. Results Across the different head and neck tumor types studied, sentinel node radiolocalization biopsy had a success rate approaching 95%. Sentinel node radiolocalization biopsy was more successful than blue-dye mapping or lymphoscintigraphy at identifying the sentinel node, although all three techniques were complementary. There was no instance of a sentinel node-negative patient developing regional lymphatic recurrence. In the head and neck squamous cell carcinoma study, there was no instance in which the sentinel node was negative and the remaining lymphadenectomy specimen was positive. Conclusion In head and neck tumors that spread via the lymphatics, it appears that sentinel node radiolocalization biopsy can be performed with a high success rate. This technique has a low false-negative rate and can be performed through a small incision. In head and neck squamous cell carcinoma, the histological appearance of the sentinel node does appear to reflect the regional nodal status of the patient. [source]

Prediction of lymphatic invasion by peritumoral lymphatic vessel density in prostate biopsy cores

THE PROSTATE, Issue 10 2008
Kenji Kuroda
Abstract BACKGROUND Lymphatic invasion in radical prostatectomy specimens has been suggested to be an unfavorable prognostic factor in clinically localized prostate cancer. Lymphangiogenesis detected by antibodies specific for lymphatic endothelial cells has been associated with lymphatic invasion and lymph node metastasis in prostate cancer. This study was designed to examine whether lymphangiogenesis in prostate biopsy could predict lymphatic spread in radical prostatectomy specimens. METHODS Paraffin-embedded positive biopsy cores obtained from 99 patients who underwent radical prostatectomy at our institution were immunostained with D2-40 monoclonal antibody, which specifically recognizes lymphatic endothelium. The association between lymphatic parameters in prostate biopsy and pathological parameters in radical prostatectomy specimens was analyzed. RESULTS Peritumoral and intratumoral lymphatic (ITL) vessels were observed in 90 (90.9%) and 23 cases (23.2%). Average and maximal peritumoral lymphatic vessel density (PTLD) and the presence of ITL in positive biopsy cores were significantly associated with positive biopsy core rates (P,=,0.0015 for average PTLD, P,<,0.0001 for maximal PTLD, and P,=,0.0038 for ITL) and lymphatic vessel invasion (P,<,0.0001 for average PTLD, P,<,0.0001 for maximal PTLD, and P,=,0.0322 for ITL). Among preoperative parameters, the biopsy Gleason score (P,=,0.0092, HR,=,6.108) and average PTLD (P,=,0.0034, HR,=,1.860) were significant predictors of lymphatic invasion in radical prostatectomy specimens in multivariate analysis. CONCLUSIONS PTLD in prostate biopsy specimens assessed by immunohistochemistry using D2-40 antibody could be a useful parameter for predicting lymphatic spread of clinically localized prostate cancer. Prostate 68:1057,1063, 2008. © 2008 Wiley-Liss, Inc. [source]

Evaluation of coxsackievirus and adenovirus receptor expression in human benign and malignant thyroid lesions

APMIS, Issue 3 2010
CONSTANTINOS GIAGINIS
Giaginis C, Zarros A, Alexandrou P, Klijanienko J, Delladetsima I, Theocharis S. Evaluation of coxsackievirus and adenovirus receptor expression in human benign and malignant thyroid lesions. APMIS 2010; 118: 210,21. Coxsackievirus and adenovirus receptor (CAR) expression on tumor cells is associated with sensitivity to adenoviral infection, being considered as a surrogate marker for monitoring and/or predicting adenovirus-mediated gene therapy. The aim of this study was to evaluate the clinical significance of CAR expression in human benign and malignant thyroid lesions. CAR protein expression was assessed immunohistochemically on paraffin-embedded thyroid tissues from 107 patients with benign and malignant lesions and was statistically analyzed in relation to histopathologic type; tumor size; lymph node metastasis; capsular, lymphatic and vessel invasion; as well as follicular cells' proliferative capacity. CAR immunoreactivity was characterized as negative/weak in 53 (49.53%), moderate in 31 (28.97%) and strong in 23 (21.50%) of 107 thyroid cases. CAR immunoreactivity was significantly increased in malignant compared with that in benign thyroid lesions (p = 0.00002). Both malignant and benign thyroid lesions with enhanced follicular cells' proliferative capacity showed significantly increased CAR immunoreactivity (p = 0.00027). In malignant thyroid lesions, enhanced CAR immunoreactivity was significantly associated with larger tumor size (p = 0.0067). The current data revealed that CAR immunoreactivity could be considered of diagnostic utility in thyroid neoplasia. Further research effort is warranted to delineate whether CAR could be considered clinically important for both diagnosis and future (gene) therapeutic applications in thyroid neoplasia. [source]

High-intensity focused ultrasound for prostate cancer: comparative definitions of biochemical failure

BJU INTERNATIONAL, Issue 8 2009
Andreas Blana
OBJECTIVES To compare the specificity and sensitivity of different definitions of biochemical failure in patients treated with high-intensity focused ultrasound (HIFU) for prostate cancer, to identify the most accurate predictor of clinical failure after HIFU. PATIENTS AND METHODS Consecutively treated patients who underwent HIFU between October 1997 and July 2006 at two centres (Lyon, France; and Regensburg, Germany) were prospectively maintained within a central database and retrospectively reviewed for this study. Clinical failure was defined as a positive prostate biopsy after treatment, radiographic evidence of lymphatic or bony metastatic disease, or salvage treatment for prostate cancer (surgery, radiation, hormonal therapy or second HIFU). The serum prostate-specific antigen (PSA) values after HIFU were assessed as a biochemical surrogate of a therapeutic success or failure. PSA threshold values, ,PSA nadir plus', PSA velocity, PSA doubling time and the American Society or Therapeutic Radiotherapy and Oncology and Phoenix definition of biochemical failure were all considered. The sensitivity, specificity, positive predictive value and negative predictive value of each biochemical definition for predicting clinical failure were determined. RESULTS The data from 285 patients (stage ,,T2, PSA <15 ng/mL, Gleason score ,7) were analysed. The median (range) follow-up was 4.7 (2,10.9) years. The median PSA nadir was 0.13 ng/mL, which occurred at a median of 12.9 weeks after HIFU, and the median PSA at the last follow-up was 0.76 (1.6,2.7) ng/mL. Clinical failure occurred in 71 patients (25%); 24 due to a positive biopsy and 47 through the use of an additional therapy. Biochemical events that best predicted clinical failure were ,PSA nadir plus' values of 1.1,1.3 ng/mL, PSA velocities of <0.3 ng/mL/year and PSA doubling times of 1.25,1.75 years. CONCLUSION A new definition of biochemical failure that is specific to patients treated with HIFU therapy is established, i.e. the ,Stuttgart definition', the ,PSA nadir plus 1.2 ng/mL'. [source]

Evaluation of the necessity for gastrectomy with lymph node dissection for patients with submucosal invasive gastric cancer

BRITISH JOURNAL OF SURGERY (NOW INCLUDES EUROPEAN JOURNAL OF SURGERY), Issue 3 2001
Dr T. Gotoda
Background: When cancer cells are found in the submucosal layer of an endoscopically resected specimen, patients are recommended to undergo gastrectomy with lymph node dissection. If it were possible to identify those patients in whom the risk of lymph node metastasis was negligible, it might be possible to avoid surgery. Methods: Among those who underwent gastrectomy for gastric cancer from 1980 to 1999, 1091 patients with a cancer invading the submucosa were studied. Clinicopathological factors (sex, age, tumour location, macroscopic type, size, ulceration, histological type, lymphatic,vascular involvement and degree of submucosal penetration) were investigated for their possible association with lymph node metastasis. Results: Lymph node metastases were found in 222 patients (20·3 per cent). Univariate analysis showed that larger tumour size (more than 30 mm), undifferentiated histological type, lymphatic,vascular involvement and massive submucosal penetration had a significant association with lymph node metastasis. Tumour size, histological type and lymphatic,vascular involvement were independent risk factors for lymph node metastasis. By combining these three factors with submucosal penetration of less than 500 ,m, 117 patients could be selected as having a minimal risk of lymph node metastasis (95 per cent confidence interval 0,3·1 per cent). Conclusion: Lymphadenectomy may not be necessary for patients with gastric cancer invading the submucosa who fulfil the above conditions © 2001 British Journal of Surgery Society Ltd [source]

A cohort study of thyroid cancer and other thyroid diseases after the Chornobyl accident,

CANCER, Issue 11 2006
Pathology analysis of thyroid cancer cases in Ukraine detected during the first screening (1998-2000)
Abstract BACKGROUND. The Ukrainian American Cohort Study evaluated the risk of thyroid disorders in a group of individuals who were younger than age 18 years at the time of the Chornobyl (Chernobyl) accident. In this article, the authors describe the pathology of thyroid carcinomas detected in the first screening. METHODS. From 1998 to 2000, 13,243 individuals completed the first cycle of screening examinations. Eighty patients underwent surgery between 1998 and 2004. Intraoperative and postoperative pathologic studies were performed at the Institute of Endocrinology and Metabolism, Kyiv. RESULTS. Pathologic analysis revealed 45 thyroid carcinomas, including 43 papillary thyroid carcinomas (PTCs) (95.6%) and 2 follicular thyroid carcinomas (FTCs) (4.4%). TNM classification (5th edition) of the PTCs included 8 T1 tumors (18.6%), 16 T2 tumors (37.2%), and 19 T4 tumors (44.2%). Fifteen PTCs (34.9%) were N1a,N1b, and 3 PTCs (7.0%) were M1. Among the PTCs, 8 exhibited the classical papillary histologic pattern (18.6%), 14 exhibited a follicular histologic pattern (32.6%), 5 exhibited a solid histologic pattern (11.6%), and 16 exhibited a mixed histologic pattern (37.2%). Both FTCs had a microfollicular-solid structure. Eleven of 20 cohort members who underwent surgery before the first screening had PTCs. Regional metastases (63.6%) and distant metastases (18.2%) were more common in this group. CONCLUSIONS. Multifocal growth, lymphatic and blood vessel invasion, extrathyroid spread, and regional and distant metastases were more frequent in less differentiated PTCs (>30% solid structure). Small carcinomas (,10 mm) comprised 23.3% of PTCs, and most of those (8 of 10 small carcinomas; 80%) were of the papillary-follicular subtype and therefore were more differentiated. The solid subtype of PTC was associated with shorter latency, especially in individuals who were diagnosed before the first screening. The histology of post-Chornobyl cancers is changing with time. Cancer 2006. Published 2006 by the American Cancer Society. [source]

Bone morphogenetic protein-10 (BMP-10) inhibits aggressiveness of breast cancer cells and correlates with poor prognosis in breast cancer

CANCER SCIENCE, Issue 10 2010
Lin Ye
Our recent study showed that a novel member of bone morphogenetic protein (BMP) family, BMP-10, was decreased in prostate cancer. In the present study, we investigated the implication of BMP-10 in breast cancer, particularly the relation of its expression with clinical aspects. The expression of BMP-10 was examined in a cohort of human breast cancer specimens (normal, n = 23; cancer, n = 97), using both quantitative real-time PCR and immunohistochemical staining. The full-length human BMP-10 was cloned into a mammalian expression plasmid vector and then transfected into breast cancer cells. The effect on growth, cell matrix adhesion, motility, and invasion of MDA-MB-231 cells by BMP-10 was then investigated using in vitro growth assays. Immunohistochemical staining and quantitative real-time PCR revealed a decreased expression of BMP-10 in breast cancer. Further analysis of BMP-10 transcript level against the clinical aspect demonstrated that the decreased BMP-10 expression correlated with disease progression, bone metastasis, and poor prognosis. The disease-free survival of the patients with a higher level of BMP-10 was 132.8 (95% CI, 122.0,143.5) months, significantly longer compared to 93.7 (95% CI, 60.3,127.2) months for patients with a lower level of BMP-10 expression (P = 0.043). The overexpression of BMP-10 has broad inhibitory effects on the in vitro growth, invasion, and motility of breast cancer cells. Taken together, BMP-10 can inhibit the cell growth of breast cancer cells, and decreased BMP-10 expression correlates to poor prognosis and disease progression, particularly the lymphatic and bone metastasis. Bone morphogenetic protein-10 (BMP-10) may function as a tumor suppressor in breast cancer. (Cancer Sci 2010) [source]

Intraductal carcinoma component as a favorable prognostic factor in biliary tract carcinoma

CANCER SCIENCE, Issue 1 2009
Hidenori Ojima
The aim of this study is to evaluate the prognostic impact of an intraductal carcinoma component and bile duct resection margin status in patients with biliary tract carcinoma. An intraductal carcinoma component was defined as carcinoma within the bile duct outside the main tumor nodule consisting of a subepithelial invasive component. Surgically resected materials from 214 patients were evaluated by histological observations. Seventy-nine patients (36.9%) with an intraductal carcinoma component infrequently developed large tumors and infrequently showed deep invasion and venous, lymphatic and perineural involvement in the main tumor nodule. An intraductal carcinoma component was inversely correlated with advanced clinical stage, and was shown to be a significantly favorable prognostic factor by both univariate and multivariate analyses. Proximal (hepatic) side bile duct resection margin status was categorized into negative for tumor cells, positive with only an intraductal carcinoma component [R1 (is)], and positive with a subepithelial invasive component (R1). Forty-five patients (21.0%) with an R1 resection margin had a poorer prognosis than 148 patients (69.2%) with a negative resection margin, whereas 21 patients (9.8%) with an R1 (is) resection margin did not. In patients with an R1 resection margin, the risk of anastomotic recurrence was higher, and the period until anastomotic recurrence was shorter, than in patients with an R1 (is) resection margin. Surgeons should not be persistent in trying to achieve a negative surgical margin when the intraoperative frozen section diagnosis is R1 (is), and can choose a safe surgical procedure to avoid postoperative complications. (Cancer Sci 2009; 100: 62,70) [source]

Histopathological features of Proteus syndrome

CLINICAL & EXPERIMENTAL DERMATOLOGY, Issue 3 2008
S. E. H. Hoey
Summary Background., Proteus syndrome is a rare, sporadic overgrowth disorder for which the underlying genetic defect remains unknown. Although the clinical course is well-described there is no systematic histopathological description of the lesional pathology. Objective., To describe the histopathological features encountered in a series of patients with Proteus syndrome from a single centre. Methods., Patients with Proteus syndrome who had undergone therapeutic surgical resection or biopsy were identified from a database and the histopathological findings were reviewed, with particular regard to descriptive features of the underlying tissue abnormality. Results., There were 18 surgical specimens from nine patients, median age 4 years (range 1,9), classified into four main categories: soft-tissue swellings (lipomatous lesions), vascular anomalies (vascular malformation and haemangioma), macrodactyly (hamartomatous overgrowth) and others (sebaceous naevus and nonspecific features). In all cases, the clinical features of overgrowth were due to increased amounts of disorganized tissue, indicating a hamartomatous-type defect in which normal tissue constituents were present, but with an abnormal distribution and architecture. Vascular malformations represented a prominent category of lesions, accounting for 50% of the specimens, predominantly comprising lymphatic and lymphovascular malformations. No malignancy or cytological atypia was identified in any case. Conclusions., The histopathological features of lesions resected from children with Proteus syndrome predominantly include hamartomatous mixed connective tissue lesions, benign neoplasms such as lipomata, and lymphatic-rich vascular malformations. [source]

Influence of parental origin of the X chromosome on physical phenotypes and GH responsiveness of patients with Turner syndrome

CLINICAL ENDOCRINOLOGY, Issue 1 2010
Jung Min Ko
Summary Objective, Previous studies have reported the effects of parental origin of the X chromosome on specific phenotypic and cognitive profiles in Turner syndrome (TS). Here, we investigate the possible parent-of-origin effects on physical phenotypes and responsiveness to GH in Korean patients with TS. Design and patients, Thirty-three patients with TS with nonmosaic karyotype and their parents participated in this study. The parental origin of the normal X chromosome was determined by comparing parental DNA polymorphisms using nine highly polymorphic microsatellite markers on the X chromosome. For the evaluation of parent-of-origin effects, typical phenotypic traits, including congenital malformations, auxological and endocrinological profiles, were compared. Results, The retained X chromosome was of maternal (Xm) origin in 60·6% patients and paternal (Xp) origin in 39·4% patients. No significant parent-of-origin effects on stature, body mass index, cardiac, renal, skeletal, lymphatic, hearing or ocular systems were evident. We observed no differences in height gain after GH treatment. In patients with the 45,X karyotype, patient height was positively correlated with maternal height in the Xm group (r = 0·60, P = 0·04). Moreover, patient height was more significantly correlated with maternal than paternal height, irrespective of the parental origin of the retained X chromosome. Conclusion, While we observed no significant impact of parental origin of the X chromosome on several phenotypic traits in patients with TS, a maternal imprinting effect on stature was suggested at least in patients with 45,X. Further studies on a larger number of patients with TS are essential to define the potential imprinting effects of undetermined genes on the X chromosome. [source]

Preoperative plasma MMP-2 expression is prognostic in colorectal cancer

COLORECTAL DISEASE, Issue 8 2006
M. G. Tutton
Introduction:, The gelatinases (MMP-2 and MMP-9) are important in colorectal cancer invasion and metastasis. Plasma concentrations of the gelatinases correlate with clinical stage in colorectal cancer; however, whether this gives prognostic information is unknown. Method:, Gelatinase mRNA and protein levels in tumour and plasma were determined respectively by RT-PCR, ELISA and gelatin zymography in a prospective study of 75 colorectal cancer patients. At follow-up, 40 patients were alive with a median survival of 75 months (range 72,80). Results:, Expression of the gelatinases was significantly increased within tumour relative to normal colon and within plasma of cancer patients (P < 0.01; Mann,Whitney U -test). Within plasma, total MMP-2 and MMP-9 expression (MMP plus MMP/TIMP complexes), determined by ELISA, and free MMP-2(72 kDa) determined by gelatin zymography, increased significantly with Dukes' stage (P < 0.001; Kruskal,Wallis test). As well as correlating with Dukes' stage, lymphatic and vascular invasion, Kaplan,Meier survival analysis showed that only elevated plasma MMP-2 was significantly associated with a worse prognosis: free MMP-2 (worse prognosis with increasing quartile; P < 0.05) and total MMP-2 (upper quartile cut-off limit; P = 0.04). Discussion:, In addition to being an indicator of colorectal cancer invasion, plasma MMP-2 levels may provide a simple, non-invasive preoperative test for prognosis in colorectal cancer. [source]

Imaging of the lymphatic system: new horizons,

CONTRAST MEDIA & MOLECULAR IMAGING, Issue 6 2006
Tristan Barrett
Abstract The lymphatic system is a complex network of lymph vessels, lymphatic organs and lymph nodes. Traditionally, imaging of the lymphatic system has been based on conventional imaging methods like computed tomography (CT) and magnetic resonance imaging (MRI), whereby enlargement of lymph nodes is considered the primary diagnostic criterion for disease. This is particularly true in oncology, where nodal enlargement can be indicative of nodal metastases or lymphoma. CT and MRI on their own are, however, anatomical imaging methods. Newer imaging methods such as positron emission tomography (PET), dynamic contrast-enhanced MRI (DCE-MRI) and color Doppler ultrasound (CDUS) provide a functional assessment of node status. None of these techniques is capable of detecting flow within the lymphatics and, thus, several intra-lymphatic imaging methods have been developed. Direct lymphangiography is an all-but-extinct method of visualizing the lymphatic drainage from an extremity using oil-based iodine contrast agents. More recently, interstitially injected intra-lymphatic imaging, such as lymphoscintigraphy, has been used for lymphedema assessment and sentinel node detection. Nevertheless, radionuclide-based imaging has the disadvantage of poor resolution. This has lead to the development of novel systemic and interstitial imaging techniques which are minimally invasive and have the potential to provide both structural and functional information; this is a particular advantage for cancer imaging, where anatomical depiction alone often provides insufficient information. At present the respective role each modality plays remains to be determined. Indeed, multi-modal imaging may be more appropriate for certain lymphatic disorders. The field of lymphatic imaging is ever evolving, and technological advances, combined with the development of new contrast agents, continue to improve diagnostic accuracy. Published in 2006 by John Wiley & Sons, Ltd. [source]

New method for evaluation of lung lymph flow rate with intact lymphatics in anaesthetized sheep

ACTA PHYSIOLOGICA, Issue 2 2006
T. Naito
Abstract Aim:, Lung lymph has commonly been studied using a lymph fistula created by tube cannulation into the efferent duct of the caudal mediastinal node in sheep. In this method, the tail region of the caudal mediastinal node is resected and the diaphragm is cauterized to exclude systemic lymph contamination, and cannulation is performed into one of the multiple efferent ducts originating from the caudal mediastinal node. Moreover, the pumping activity of lymphatics might be diminished by cannulation. Therefore, the purpose of the study was to evaluate the flow rate of lung lymph with maintenance of intact lymphatic networks around the caudal mediastinal node to the thoracic duct in sheep. Methods:, An ultrasound transit-time flow meter was used to measure lung lymph flow. The thoracic duct was clamped just above the diaphragm and the flow probe was attached to the thoracic duct just after the last junction with an efferent duct from the caudal mediastinal node. The lung lymph flow rate was measured at baseline and under conditions of lung-oedema formation. Results:, The baseline lung lymph flow rate in our model was three- to sixfold greater than values obtained with the cannulation method. With oedema-formation, the lung lymph flow rate was the same as that measured using cannulation. Conclusion:, The lung lymph flow was unexpectedly large under the conditions of the study, and our data suggest that the drainage effect of lymphatics is significant as a safety factor against pulmonary oedema formation. [source]