跳至主要内容
临床试验/NCT03465930
NCT03465930Unknown不适用

Histologic Analysis of the Lymphatic Collecting Vessels Used for Minimally Invasive Supermicrosurgical Lymphatico-venous Anastomoses in the Treatment of Lymphedema

Paolo Gennaro1 个研究点 分布在 1 个国家目标入组 200 人开始时间: 2017年6月1日最近更新:
适应症

试验速览

阶段
不适用
发起方
入组人数
200
试验地点
1
主要终点
Expression of the lymphatic endothelial marker D2-40 in relation with the duration of lymphedema.

研究概览

简要总结

Lymphedema, primary or secondary, is a chronic disease that causes functional impairment and has an important impact on patient's quality of life. Lymphedema can be primary or secondary. Secondary lymphedema, which is more common, especially in industrialized countries, is often due to surgery and radiotherapy to treat cancer. There is no definite cure for lymphedema; conservative treatments such as elastic compression garments, bandages and manual lymphatic drainage help reducing the edema but do not resolve it. Many types of surgery have been used in the past, the most recent are lymphatic-venous anastomoses, a minimally invasive procedure that may be performed under local anesthesia. Briefly, after visualizing the lymphatic vessels with a fluorescent dye, one or more anastomosis are created between collecting lymphatic vessels and superficial veins in order to drain the lymph into the blood stream bypassing the obstacle. During this procedure, it is possible to take samples of the collecting lymphatic vessels that are to be anastomosed with veins and use them for histological and immunohistochemical studies, without causing any additional discomfort to the patient. These samples can be formalin fixed and paraffin embedded. The obtained sections will be stained with a lymphatic endothelium marker and a smooth muscle specific stain. A morphometric study will be conducted and, based on the results a statistical evaluation will be made. The analysis will be conducted on samples obtained from patients, affected by secondary or primary lymphedema willing to provide their free and informed consent. The aim of this study is to evaluate the histopathological characteristics of the collecting lymphatic vessels that have been anastomosed with adjacent veins during surgery, and relate the results with the obtained clinical response. The acquired knowledge will contribute to optimize the clinical approach to prevent and treat lymphedema, by helping to select the patients that will benefit more from the surgery, and to select vessels and anatomical sites that have better chances to provide efficient anastomoses.

详细描述

Background:

Lymphedema is a chronic pathologic condition that causes significant functional impairment to the patient and has a great impact on his quality of life. It may be primary or secondary. Secondary lymphedema, that is the most common, is generally due to surgery and radiotherapy for cancer, particularly of the breast, uterus and prostate but can also occur after a trauma. Primary lymphedema can be congenital or begin at puberty, or more rarely after age 35, in this case, often following a trigger event such as trauma or infection.

There is no specific treatment for this highly disabling disease and patients must lifelong try to reduce edema and limit its progression by the use of elastic compression garments and with manual lymphatic drainage. Over the years several surgical approaches have been proposed, including more recently super microsurgical lymphatic-venous anastomosis (sLVA) to allow drainage of the lymph in the venous stream distal to the obstruction. sLVA is a minimally invasive procedure performed under local anesthesia with discharge the day after surgery. It requires an accurate visualization of the lymphatic vessels that are still functional. Lymphatic vessels are visualized with lymphography using a fluorescent dye, indocyanine green. In selected cases, magnetic resonance can also be useful. Small samples of the vessel selected to perform the LVA can easily be taken during surgery, formalin-fixed and paraffin-embedded for histologic and immunohistochemical studies without further discomfort or complications for the patient.

Knowledge on the histopathological aspects of lymphedema is extremely limited, this study must therefore be considered an exploratory one, possibly intended to generate more hypotheses than to solve them. A better understanding of the physio-pathological mechanisms of lymphedema can lead to a more effective surgical approach and, in selected cases, even prevent its development with considerable advantages in terms of the patient's quality of life and also in reducing national health care system costs (direct costs arising from the need to undergo continuous physiotherapy and indirect costs due to disability, serious intercurrent infections requiring hospitalization and loss of work days).

Primary purpose of the study is to evaluate the histopathologic features of the lymphatic vessels anastomosed with veins. The primary purpose will be divided in two phases: 1. on secondary lymphedema; 2. on primary lymphedema.

研究设计

研究类型
Observational
观察模型
Case Only
时间视角
Cross Sectional

入排标准

年龄范围
18 Years 至 —(Adult, Older Adult)
性别
All
接受健康志愿者

入选标准

  • age over 18 years old;
  • patients affected by primary or secondary lymphedema;
  • patients willing to give their free and informed consent.

排除标准

  • patients currently undergoing radiotherapy;
  • patients currently undergoing chemotherapy.

结局指标

主要结局

Expression of the lymphatic endothelial marker D2-40 in relation with the duration of lymphedema.

时间窗: Collection of samples from different sites of at least 10 patients will require at least 6 months

On sections stained with D2-40, under light microscopy with the aid of the morphometric program NIS elements tracing the portions of the endothelium stained positively for this marker and comparing the sum of all positive segments of each vessel with the length of its inner profile. The duration of lymphedema in number of years can be obtained using previous medical records (e.g. lymphography or lymphoscintigraphy) when the patient comes to observation after the diagnosis has already been made or, when no previous medical record is available, through the anamnesis. The duration of lymphedema from clinical onset to the time of surgery is expressed in number of years.

次要结局

  • Relation between the anatomic site of the anastomosis and histologic parameters.(Collection of samples from different sites of at least 10 patients will require at least 6 months.)
  • Area of the vessel wall versus area of the lumen(Collection of samples from different sites of at least 10 patients will require at least 6 months)
  • The relative proportion of smooth muscle cells and collagen fibers in the lymphatic vessel wall.(Collection of samples from different sites of at least 10 patients will require at least 6 months)
  • Differences in the histology of lymphatics between primary and secondary lymphedema.(Since primary lymphedema is rare, collection of an adequate number of cases of primary lymphedema (at least 10) to evaluate whether there are histologic differences with secondary lymphedema will require at least three years.)
  • Correlation between histologic modifications and morphologic appearance at lymphography and / or at MRL (Magnetic Resonance Lymphography).(Collection of samples from different sites of at least 10 patients will require at least 6 months)

研究者

发起方
Paolo Gennaro
申办方类型
Other
责任方
Sponsor Investigator
主要研究者

Paolo Gennaro

MD, PhD. Associate Professor of Maxillofacial Surgery, University of Siena

University of Siena

研究点 (1)

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