A Case of Hepatopulmonary Syndrome Solved by Mycophenolate Mofetil (An Inhibitor Of Angiogenesis and Nitric Oxid Production).

Oct 2012

Silva HM, Reis G, Guedes M, Cleto E, Vizcaíno JR, Kelly D, Gennery AR, Silva ES.

Source

Pediatric Gastroenterology Unit, Department of Child and Adolescent, Centro Hospitalar do Porto, Portugal.

Abstract

BACKGROUND:

The autoimmune lymphoproliferative syndrome (ALPS) is a rare, multi-systemic disease, caused by an inherited defect in the Fas apoptotic pathway, characterized by a chronic non-malignant lymphoid accumulation, andautoimmune manifestations. Lung, kidney, liver, and gut infiltration is described in severe, multi-systemic cases; so far there is no description of hepatopulmonary syndrome (HPS), for which orthotopic liver transplantation (OLT) is currently the only known effective treatment.

CASE REPORT:

 A Teenage boy, diagnosed with ALPS at 4 years old (lymph nodes enlargement, splenomegaly, immune cytopenias), was stable until 13 years old when he developed insidiously hypoxemia (PaO2 = 46.7 mmHg). He was diagnosed with HPS on the basis of hypoxemia, non-cirrhotic liver disease with portal hypertension, and pulmonary vascular dilatation (intra-pulmonary shunt = 45%). He was treated with oxygen (maximum 6 liters/minute), prednisolone and sirolimus. There was significant regression of all manifestations of ALPS, except the pulmonary symptoms, so, after evaluation in referral centers in England, OLT was proposed. Since he was to be submitted to major surgery, sirolimus, which has wound healing problems, was switched for mycophenolate mofetil (MMF). Following this change, we observed an enormous improvement of the pulmonary symptoms and reduction of oxygen needs. The intra-pulmonary shunt decreased from 45% to 0% in less than a year, and remains so until today (18 months after complete normalization), on continued treatment with MMF. Indication for OLT was suspended. In the last year lymphoid proliferation increased again, with huge splenomegaly, but no recurrence of HPS. The addition of sirolimus to MMF produced again a rapid resolution of lymphoid proliferation.

CONCLUSION:

The dramatic and unexpected regression of HPS may have been due to inhibition of angiogenesis and nitric oxide (NO) production by MMF (both important pathways/mediators in the HPS pathogenesis). Therefore, we propose the conduct of clinical trials with MMF, and/or other angiogenesis and NO inhibitors, in a long-term treatment basis, to confirm their potential as a valid alternative for medical treatment of HPS.

Elsevier

Lymphatics, lymph nodes and the immune system: barriers and gateways for cancer spread.

Oct 2012

Ferris RL, Lotze MT, Leong SP, Hoon DS, Morton DL.

Source

Hillman Cancer Center Research, Pavilion 5117 Centre Avenue, Room 2.26b, Pittsburgh, PA, 15213, USA, ferrisrl@upmc.edu.

Abstract

Metastasis to the regional lymph node is the most important prognostic indicator for the outcomes of patients with sold cancer. In general, it is well recognized that cancer development is genetically determined with progression from the microenvironment of the primary tumor site, oftentimes via the SLN gateway, to the distant sites. In about 20 % of the time, the cancer cells may spread directly through the blood vascular system to the distant sites. Thus, in general, cancer progression is consistent with Hellman's spectrum theory in that development of nodal and systemic metastasis from a localized cancer growth is a progressive process. 

Cancer proliferation within the tumor microenvironment may give rise to increased tumor heterogeneity, which is further complicated by its continuous change through its evolution within the host in a Darwinian sense. It is crucial to understand the molecular process of lymphangiogenesis and hemangiogenesis in the tumor microenvironment with respect to the initial steps of cancer cells entering into the lymphatic and vascular systems so that rational therapy can be developed to curb the process of specific routes of metastasis. This chapter elucidates the role of lymphatics, nodal metastasis and antitumor immunity. 

We present novel immune targets in nodal metastases, the importance of the lymph node as a pre-metastatic niche, and immune-related proteins as biomarkers of metastasis.

PubMed

Understanding the Lymph System

Understanding the Lymph System

I thought it would be helpful for readers to understand the lymph system, the anatomy, what it does, and how it helps with immunity.

Listed below are information pages that should be quite helpful and each page has many additional links for more a more in depth study.

Anatomy of the Lymph System

Lymphatic System Functions

Lymphatic System and Immunity

Pathology of the Lymph Nodes and Lymphoma

Lymph Nodes

Lymph Fluid

Cervical lymph nodes

Cervical lymph nodes

Eur J Radiol. 2008 Mar 10

Mack MG, Rieger J, Baghi M, Bisdas S, Vogl TJ.
Department of Diagnostic and Interventional Radiology, University Hospital Frankfurt, Johann Wolfgang Goethe-University, Theodor-Stern-Kai 7, 60590 Frankfurt/Main, Germany.

The lymph node staging is a very important prognostic parameter for patients with presenting with head neck cancer and is influencing the selection of the different therapeutic strategies including surgery, chemotherapy, radiotherapy or a combination of them. The accuracy of imaging techniques, such as US, MR imaging, and CT, depends on the appropriateness of radiological criteria used for diagnosing lymph node metastases. Size of nodes and evidence of necrosis are still the most important radiological criteria. However, the size shows great variability. A spherical lymph node larger than 10mm is an indicator for a malignant node, whereas an oval shape and/or a fatty hilus are more benign signs. But there are many limitations and different cut offs published in the literature, indicating that the size of a lymph node is not a reliable criteria for the assessment of lymph nodes in the head and neck region. Today new high-resolution MRI sequences and the development of specific contrast agents are offering new possibilities in the diagnostic work-up of head and neck lymph nodes. Ultrasmall superparamagnetic iron oxide particles (USPIO's) are resulting after intravenous application in a reduction of the T2 relaxation time. This is causing a signal decrease on T2-weighted MR images in benign lymph nodes after administration of USPIO's, whereas malignant lymph nodes do not show a significant signal decrease. Some clinical studies presented already very promising results. Based on the fact, that the size evaluation of lymph nodes in the head and neck has not changed during the last decade, this paper will mainly focus on MRI with new contrast agents and new techniques as diffusion weighted imaging (DWI).

PMID: 18337039 [PubMed - as supplied by publisher]