Disorders of the Lymph System

Subject: Organization and developmental aspects of lymphatic vessels.
Time: 1:38:03 AM EDT
Author:  patoco2

Organization and developmental aspects of lymphatic vessels.

Arch Histol Cytol. 2008 Mar

Ohtani O, Ohtani Y.

Department of Anatomy, Faculty of Medicine and Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama.

The lymphatic system plays important roles in maintaining tissue fluid homeostasis, immune surveillance of the body, and the taking up dietary fat and fat-soluble vitamins A, D, E and K. The lymphatic system is involved in many pathological conditions, including lymphedema, inflammatory diseases, and tumor dissemination. A clear understanding of the organization of the lymphatic vessels in normal conditions would be critically important to develop new treatments for diseases involving the lymphatic vascular system. Therefore, the present paper reviews the organization of the lymphatic vascular system of a variety of organs, including the thyroid gland, lung and pleura, small intestine, cecum and colon in the rat, the diaphragm in the rat, monkey, and human, Peyer's patches and the appendix in the rabbit, and human tonsils. Methods employed include scanning electron microscopy of lymphatic corrosion casts and tissues with or without treatment of alkali maceration technique, transmission electron microscopy of intact tissues, confocal microscopy in conjunction with immunohistochemistry to some lymphatic-specific markers (i.e., LYVE-1 and VEGFR-3), and light microscopy in conjunction with enzyme-histochemistry to 5'-nucleotidase. Some developmental aspects of the lymphatic vessels and lymphedema are also discussed.

Archives of Histology and Cytology

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Subject: Advocates for Lymphedema
Time: 6:07:10 AM EDT
Author:  patoco2

===============================================

Join us as we work for lymphedema patients everywhere:

Advocates for Lymphedema

Dedicated to be an advocacy group for lymphedema patients. Working towards education, legal reform, changing insurance practices, promoting research, reaching for a cure.

http://health.groups.yahoo.com/group/AdvocatesforLymphedema/

To Subscribe

AdvocatesforLymphedema-subscribe@yahoogroups.com Join us today to learn about, for daily discussions and for advocacy on behalf of lymphedema.

Pat O'Connor

Lymphedema People / Advocates for Lymphedema

==============================================

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Subject: Hemorrhagic mesenteric cystic lymphangioma presenting with acute lower abdominal pain
Time: 8:53:09 AM EDT
Author:  patoco2

Hemorrhagic mesenteric cystic lymphangioma presenting with acute lower abdominal pain: the diagnostic clues on MR Imaging.

Emerg Radiol. 2008 Jul 5

Okamoto D, Ishigami K, Yoshimitsu K, Irie H, Tajima T, Nishie A, Hirakawa M, Ushijima Y, Nishihara Y, Kakeji Y, Honda H.

Department of Clinical Radiology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan, dokamoto@med.kyushu-u.ac.jp.

A 32-year-old woman complained of acute lower abdominal pain. Computed tomography showed a complex multilocular cystic mass at the right adnexal region. Magnetic resonance imaging demonstrated the origin of the mass to be the small bowel mesentery. Chemical-shift images detected septal fat of the cystic mass and suggested a small amount of fat within the locules of the cyst. A cystic tumor of the mesentery such as cystic lymphangioma, hemangioma, cystic mesothelioma, and dermoid was included in the differential diagnoses. The diagnosis of a hemorrhagic mesenteric cystic lymphangioma was confirmed at surgery and pathologic analysis. Cystic lymphangioma should be included in the differential diagnosis of acute abdominal pain. The detection of septal fat may be helpful in the diagnosis of cystic lymphangioma when it shows unusual radiological appearances.

Springerlink

Tags: Cystic lymphangioma; Acute abdominal pain; cystic mesothelioma; Fat component; Magnetic resonance imaging (MRI); cystic tumor ; Chemical-shift image

Subject: Important changes on Lymphedema People
Time: 8:43:04 AM EDT
Author:  patoco2

Important changes on Lymphedema People

Happy Fourth of July

I did want to advise everyone on some important changes on Lymphedema People.

I have put out a number of new Wiki pages in the last week. There is a page you can go to to see any new or revised articles:

New Articles and Updates

You can also "subscribe" to this page and automatically be advised when new articles and updates are posted. When you go to the page, scroll way down and click on the "RSS/XHL Feed" on the left bottom corner. 

That takes you to a page where at the top in a yellow background panel you can subscribe to that page. Click on
the "Subscribe to the feed" line.

On the new website entry page:

http://www.lymphedemapeople.com/

Search

We now have a search line that finally brings together the ability to search all HTML articles; Wiki pages and the Forums. When you enter a term on that lines, now no matter where on the entire site a subject is, you will finally be able to find it.

Translate

While translation technology still has a long way to go, Google has the best tool available. Below the search line is a new translation device. We literally have several thousand people a week visiting the website from around 130 countries. This translation device will translate 24 languages other then English When a language is chosen, the website will change and come back up in the chosen language.

I am excited about this as it helps so many more people will have access to lymphedema information in their native language.

This is what it is all about folks.

I hope you enjoy the new features.

Pat

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Subject: Natural history of pelvic lymphocysts as observed by ultrasonography after bilateral pelvic lymphade
Time: 10:04:11 PM EDT
Author:  patoco2

Natural history of pelvic lymphocysts as observed by ultrasonography after bilateral pelvic lymphadenectomy.

Ultrasound Obstet Gynecol. 2008 Jun

Tam KF, Lam KW, Chan KK, Ngan HY.

Gynaecological Oncology Division, Department of Obstetrics and Gynaecology, The University of Hong Kong, Queen Mary Hospital, Hong Kong SAR, China.

OBJECTIVES: To determine, in patients who have undergone bilateral pelvic lymphadenectomy for gynecological cancer, the incidence of lymphocyst formation, their change in size with time, risk factors and correlation with symptoms.

METHODS: This was a prospective observational study of 108 patients undergoing bilateral pelvic lymphadenectomy for gynecological cancer in our unit. We performed serial three-dimensional (3D) ultrasound assessment at 2 and 6 weeks and 3, 6, 9 and 12 months after surgery. Before each ultrasound assessment, symptoms were recorded and a physical examination was performed.

RESULTS: Forty-eight (44.4%) patients had unilateral or bilateral lymphocysts detected during the follow-up period; 26 were on the left side, 16 were on the right side and six were bilateral. In 39 (81.2%) of the patients, the lymphocysts were first noted 2 weeks after the operation. In nine (18.8%) the lymphocysts persisted until 12 months after surgery. There was no association between lymphocyst formation and diagnosis, type of operation performed, surgeon, operative blood loss, adjuvant radiotherapy and number of lymph nodes removed. Four lymphocysts were detected by physical examination before the ultrasound diagnosis. There was no association between lymphocyst and symptoms, including pain over the abdomen, pelvis, thigh, legs or back, lymphedema, fever or symptoms of cystitis. Only one patient developed an infection of the lymphocyst, which required surgical intervention.

CONCLUSION: Lymphocyst formation is common following bilateral pelvic lymphadenectomy. Most patients with lymphocysts are asymptomatic and the development of major complications is rare.

Wiley InterScience

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Subject: Sentinel lymph node biopsy for the detection of lymph node micrometastasis in early lung cancer
Time: 6:22:42 AM EDT
Author:  patoco2

Usefulness of sentinel lymph node biopsy for the detection of lymph node micrometastasis in early lung cancer.

Interact Cardiovasc Thorac Surg. 2008 Jun 5

Sugi K, Kobayashi S, Yagi R, Matsuoka T.

National Sanyo Hospital, Ube, Japan.

The purposes of this study were to examine the usefulness of the biopsy of the sentinel lymph nodes (SNs) for the accurate and effective detection of lymph node micrometastasis in early lung cancer and to clarify the spread of lymph node micrometastasis. 133 c-stage IA non-small cell lung cancer patients in whom SNs could be identified by RI method were enrolled. All dissected lymph nodes were stainedwith with cytokeratin AE1/AE3 for the examination of micrometastasis. A total of 1375 lymph nodes including 220 SNs were dissected from the 133 patients. From the 220 SNs, 35 (15.9%) were found to be positive for metastasis. Of the other 185 SNs negative for metastasis, 19 (8.6%) were positive for micrometastasis. When patients were limited to those with pN0, there were no lymph nodes positive for micrometastasis other than SNs. In pN1-2 patients, micrometastasis to non-SNs were observed in 2.3-13.2%. In patients with pN0, micrometastasis was limited to SNs, and the results of the examination of SNs for micrometastasis accurately represented those of the examination of all lymph nodes. With advancement of the stage, micrometastasis was not limited to SNs and showed an irregular distribution.

Interactive Cardiovascular & Throacic Surgery

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Subject: Lymphedema People forums
Time: 2:46:42 PM EDT
Author:  patoco2

Good afternoon ya'll.

I wanted to let everyone know that we have brand new forums on Lymphedema People.

If you have the forums page saved on your PC, you'll need to "refresh" your page.

Important - if you were a member of the old forums, you were automatically transferred to the new ones - and all you have to do is sign on like you normally do.

You can access the new forums by going to

http://www.lymphedemapeople.com/wiki/doku.php

Look down the page a little bit and you'll see "Forums" just click on that link and you'll be taken there.

The new forum URL is:

http://www.lymphedemapeople.com/phpBB3/

The new forums tie in directly with the new Wiki - making them more integrated and will in the long term make things better.

Thanks!!!!

BTW....if you haven't visited and joined the forums...this is a perfect time to do it. 

We have - 145 articles/pages on the Wiki

340 on the HTML format (the ones I've been updating) and...... 1,297 topics on the forums. 

The forums also offer the largest single site on information for lymphatic conditions not only in English, but in French and Spanish as well.

Pat

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Subject: B-cell lymphoma with febrile inflammatory lymphoedema of the lower limbs and lower back
Time: 6:11:12 AM EDT
Author:  patoco2

B-cell lymphoma with febrile inflammatory lymphoedema of the lower limbs and lower back

Ann Dermatol Venereol. 2008 Apr

Pallure V, Dandurand M, Stoebner PE, Habib F, Colonna G, Meunier L.

Service de dermatologie, groupe hospitalo-universitaire Carémeau, rue du Professeur-Robert-Debré, 30900 Nîmes, France.

BACKGROUND: Intravascular lymphomas are diffuse large-cell lymphomas belonging to a group of high-grade non-Hodgkin's lymphomas and are generally of phenotype B. They are rare and carry a severe prognosis. Clinical polymorphism is dominated by neurological and cutaneous involvement.

PATIENTS AND METHODS: We report the case of an 80-year-old woman with cutaneous intravascular B-cell lymphoma as revealed by an isolated episode of febrile bilateral inflammatory lymphoedema. Following combined chemotherapy with rituximab and mini-CHOP (cyclophosphamide, adriamycin, oncovin and prednisone), complete remission was obtained rapidly, with no relapse at two years.

DISCUSSION: Diagnosis of these tumors is rendered difficult by the clinical polymorphism and multifocal nature of lymphocytic proliferations. In the present case, diagnosis was based on histology results since presentation of the disease in the form of bilateral inflammatory oedema of the lower limbs is not sufficient to establish lymphoma. Combined rituximab and polychemotherapy comprising a CHOP regimen appears to yield the best results.

Keywords: Intravascular B-cell lymphoma; Lymphedema

Elsevier

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Subject: The potential effect of statins on rituximab immunotherapy.
Time: 10:44:25 AM EDT
Author:  patoco2

The potential effect of statins on rituximab immunotherapy.

Mark S. Cragg

Abbreviations: ADCC, antibody-dependent cellular cytotoxicity; CDC, complement-dependent cytotoxicity; HMG-CoAR, 3-hydroxy-3-methylglutaryl-coenzyme A reductase; mAb, monoclonal antibody

Mark Cragg is in the Cancer Sciences Division, University of Southampton, Southampton, United Kingdom. E-mail: msc@soton.ac.uk

Background

CD20 is a cell surface marker expressed on mature B cells and most malignant B cells. It does not modulate rapidly, is not shed, and is highly expressed, leading to its use as a target for immunotherapy. In 1997, rituximab, a chimeric anti-CD20 monoclonal antibody (mAb), was approved for use in the treatment of cancer following its efficacy (46% response rate) in a phase II trial involving 37 patients with relapsed low-grade non-Hodgkin lymphoma . Since then, rituximab has been approved for the treatment of numerous other B cell malignancies and is now being actively investigated for use in the treatment of autoimmune disorders such as rheumatoid arthritis and systemic lupus erythematosus . As a result, rituximab has been administered to more than a million patients worldwide, making it the most successful immunotherapeutic (commercially and clinically) used to date.

Importantly, much of the therapeutic efficacy of rituximab is seen when it is used in combination with other drugs. In the treatment of non-Hodgkin lymphoma, rituximab is routinely given in conjunction with chemotherapy, which greatly enhances the therapeutic outcome in terms of response rates, durations of remissions, and improvements in survival . A similar synergy is observed between rituximab and cyclophosphamide or methotrexate  in the treatment of autoimmune conditions. In part, these effective combinations are afforded bythe distinct toxicity profiles of the different drugs and the relatively mild side effects observed with rituximab treatment. For these reasons rituximab is an ideal drug for investigating powerful combination therapies.

One group of drugs that could potentially be useful in combination with rituximab is the statins. Statins target 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMG-CoAR), which is the rate-limiting enzyme of the mevalonate pathway required for the synthesis of isoprenoids such as cholesterol. As such, the main clinical use of statins to date has been in the treatment of hypercholesterolemia. However, in addition to inhibiting cholesterol synthesis, statins also have cytotoxic effects on tumor cells  These cytotoxic effects are likely achieved through one of two downstream effects of HMG-CoAR inhibition. First, by reducing isoprenoid synthesis, statins impair protein prenylation, a critical process for the correct cellular localization and signaling activity of numerous proteins such as Ras that may be important for tumor cell survival. Second, reducing cholesterol synthesis can interfere with the formation of cholesterol-rich lipid microdomains, or “rafts,” within the plasma membrane. These lipid rafts are thought to represent localized signaling platforms and may be particularly important in providing cell survival signals to tumor cells . Moreover, as prenylated proteins commonly localize to lipid raft regions, statin treatment may therefore doubly compromise the biological activity of these proteins, providing potent cytostatic and cytotoxic effects. Clearly statins have an obvious anti-tumor potential, and it seems sensible to consider whether they provide a useful drug combination in conjunction with rituximab.

Statins Decrease the Efficacy of Anti-CD20 mAb by Preventing Their Binding

In a new study published in this issue of PLoS Medicine, Jakub Golab and colleagues address this very issue: namely, how do statins affect rituximab treatment? Perhaps surprisingly, they show that instead of enhancing the ability of rituximab to kill target cells, statins are inhibitory.

Rituximab has three main effector mechanisms: Complement-dependent cytotoxicity and antibody-dependent cellular cytotoxicity (CDC and ADCC, respectively) and direct cytotoxic signaling. Using a number of well-established in vitro assays, Golab and colleagues clearly show that statins impair the ability of rituximab to lyse lymphoma cell lines with the help of either complement (CDC) or, to a lesser degree, effector cells (ADCC), and that this impairment occurs because surface binding of CD20 is greatly reduced in these cells . The researchers did not examine the ability of statins to inhibit direct cytotoxic signaling, but presumably this was also reduced due to diminished mAb binding. Therefore, at least two (and likely all) of the main effector mechanisms of rituximab were reduced by statin treatment. After establishing that the loss of CD20 binding was due to a change in conformation of surface CD20 after statin treatment, the authors then performed experiments to examine the effect of statins on CD20 in vivo. Although the effects here were more marginal, again the evidence suggests that statins reduce the binding of rituximab to its target.

Statins as a Contraindication for Rituximab Treatment?

Given the potential implications of these findings, the next steps are to confirm them and then to establish the CD20 status of patients on long-term statin treatment. Subsequently, it will be important to address whether equivalent effects on CD20 binding are observed in patients suffering from malignant or autoimmune disease to determine whether B cells in these conditions are more or less susceptible to the effects of cholesterol depletion through statin treatment. Previous in vitro experiments with methyl-beta-cyclodextrin indicate that the effects of cholesterol depletion on CD20 mAb binding are highly dependent upon both the mAb and cell type. Presumably, data on the effects of statins on rituximab use are already available through retrospective analysis, as it is likely that among the million patients treated with rituximab a proportion were also receiving statins. To date, very few cases of co-administration have been reported, but it is important to note that in at least one of these, long-term statin treatment did not appear to impair the normal therapeutic effect of rituximab . These data, coupled with the limited effects seen in Figure 9 of Golab andcolleagues' study , suggest that the pronounced effects of statin treatment on anti-CD20 binding observed on lymphoma cell lines in vitro may not translate to equivalent effects in vivo. However, note that the CD20 binding shown in  was assessed after only a three day treatment with atorvastatin; potentially greater effects would be observed after more protracted treatment. The definitive answer to the question of whether statins substantially affect CD20 binding and function in vivo awaits clinical investigation.

Assuming long-term statin treatment does indeed substantially reduce CD20 detection in vivo, two obvious changes to clinical management should be made. First, extensive use of statins for the treatment of hypercholesterolemia should be a contraindication for the use of CD20 as a diagnostic marker for mature B cells. Second, statins should be removed from the treatment of patients with either malignant or autoimmune disease who are required to undergo CD20-specific therapy.

Other Combinations?

Interestingly, Golab and colleagues reported (but did not show) that inhibitors of farnesyltransferase and geranylgeranyltransferase did not decrease CD20-mediated CDC , indicating that the effect of statins on anti-CD20 mAb binding is independent of their effects on impaired protein prenylation. As prenylation inhibition is a central component of the anti-tumor effect of statins, it is possible that farnesyltransferase and geranylgeranyltransferase inhibitors such as tipifarnib may work well in combination with rituximab. To discover if this is the case, a sensible way forward would be to examine the direct cell-killing activity of these reagents in combination with rituximab. Whether this combination will also fall foul of unexpected complications remains to be seen.

PLOS Journals

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Subject: Re-emergence of lymphogranuloma venereum.
Time: 10:48:54 PM EDT
Author:  patoco2

J Eur Acad Dermatol Venereol. 2008 Apr

Kapoor S.

glossomed@gmail.com

Keywords: anal strictures, chlamydia trachomatis, genital ulcers, inguinal lymphadenopathy, proctitis

Lymphogranuloma venereum (LGV) is a sexually transmitted infection caused by the L1, L2 and L3 serotypes of Chlamydia trachomatis. The disease has been in the spotlight recently because of recent outbreaks in Europe as well as the USA. A unique feature of the recent outbreaks has been that most cases have been caused by the L2 strain. Another unique feature of these outbreaks is the fact that most cases have occurred in men having sex with men, and most patients have presented with proctitis. Interestingly, most recent cases have occurred in human immunodeficiency virus-seropositive patients. Usually, the disease is divided into three phases: the primary stage characterized by a self-healing papule, the secondary stage characterized by proctitis or lymphadenopathy and the tertiary stage characterized by lymphedema and anal strictures. Tests used for diagnosis include polymerase chain reactions and compliment fixation tests. The treatment of choice is doxycycline.

Blackwell

Tags: lymphogranuloma venereum, Chlamydia trachomatis, proctitis, lymphadenopathy, doxycycline, genital ulcers,

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