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Defects in angiogenesis occurring in utero produce a broad spectrum of clinical abnormalities. Some regress in infancy, some persist and may be allied with abnormalities of other structures. The possible interrelationships between abnormalities of the arterial, venous and lymphatic systems and skeletal development are explored in this paper.
A 72 year old female was admitted for an operation of gastric cancer. At the operation, a 3 x 3 cm-sized, whitish and multilocular nodule was incidently found at the left side of the spleen. This nodule was adjoining the splenic capsule and was characterized with sparsely found multilocular lymphatic cysts with varying sizes. The walls of these cysts were composed of partly thin fibrous tissue, or partly thin to thick splenic trabeculae. Abnormally elongated, nodular or fragmentary trabeculae were also present in the nodule. White and red splenic pulp was found widely dispersed among the cysts. The surrounding splenic tissue was not compressed. We considered the essence of this tumor to be an abnormal mixture of normal splenic elements such as lymphatics, splenic trabeculae, and red and white pulp, and regarded this tumor as a focal malformation (lymphangiomatous hamartoma) rather than a true neoplasm such as a lymphangioma.
UNLABELLED: Primary intestinal lymphangiectasia induce symptoms of protein-losing gastroenteropathy. Only very few studies evaluate the long term follow up of such patients. We reviewed six children diagnosed at 17 +/- 12 months and followed for 11 +/- 4.9 years. CASE REPORTS: As soon as the diagnosis was made the patients were submitted to a strict low fat diet with added medium chain triglycerides and intermittent liposoluble vitamins perfusions. The diet allowed the disappearance of symptoms for all the patients but laboratory findings indicated continuing chyle leak for most of the children. Only one child who had normal biological parameters tolerates a normal diet since four years. Relaxation of the diet by two patients who had moderate hypoalbuminemia and lymphopenia led to severe clinical relapses 14 and 17 years after the diagnosis period with therapeutic difficulties. Three patients with long term strict low fat diet remain asymptomatic. CONCLUSION: In most asymptomatic patients, the underlying lymphatic defect remains with permanent biological abnormalities. Clinical relapses may be severe and difficult to treat; thus the need for dietary treatment appears to be permanent.
A 20-year-old Persian man with Middle Eastern lymphoma is described, and 84 additional cases from the literature are reviewed. Basically, the disease is a malignant lymphoma which involves the upper small intestine (duodenum and proximal jejunum). It is associated with clubbing of the fingers, abdominal pain, weight loss, diarrhea, vomiting, and malabsorption, and frequently occurs in a younger age group than "Western Hemisphere" intestinal lymphoma. Some patients also have alpha heavy chain disease. The sex ratio is equal, and the disease occurs only in Middle Eastern and North African Moslems and Jews. Upper gastrointestinal radiographs are frequently diagnostic, and per oral small intestinal biopsy is nearly always diagnostic. Pathologically, the following features are characteristic for Middle Eastern lymphoma: partial or total villous atrophy with only mildly abnormal surface epithelium, sparsity of crypts, lymphatic dilatation, and infiltration of lamina propria by pleomorphic mononuclear cells which pepetrate the muscularis mucosa. The etiology and pathogenesis of this disease are unknown, but several hypotheses are discussed. Treatment by a variety of modalities is far from satisfactory, and the prognosis is much poorer than that observed in patients with the "Western" form of intestinal lymphoma. Other differences between Middle Eastern lymphoma and Western lymphoma are described in detail,
Seven patients with lymphoedema of the hands and arms, an unusual extra-articular feature of rheumatoid arthritis, are described. In all cases the lymphoedema persisted throughout follow up--in one case for more than five years--and was resistant to treatment with slow acting drugs, steroids, or cytotoxic agents. There was no correlation with severity of disease. It is concluded that the lymphoedema in these patients may be associated with reduced numbers of lymphatic vessels; increased capillary permeability or abnormal fibrinolysis may also be contributory factors. Conservative management of such patients is recommended.
Cardiac disease associated with congestive heart failure was found to be the most common cause (22 of 76) of pericardial effusion in patients referred for echocardiography. Parameters of left heart function were markedly abnormal in these patients with congestive heart failure and pericardial effusion, but were not significantly different from a group of patients with congestive heart failure without pericardial effusion. Clinical findings consistent with cardiac decompensation also failed to discern between these two groups. Nonetheless, patients with congestive heart failure with pericardial effusion had significantly larger right ventricular internal dimensions than those without effusion. Patients with pericardial effusion related to congestive heart failure (P < .01), heart disease without congestive heart failure (P < 0.001) and those patients post recent myocardial infarction (P < 0.05) had significantly larger right ventricular internal dimensions in diastole than normal subjects. Patients with pericardial effusions related to recent open heart surgery, idiopathic pericarditis or of miscellaneous causes had normal right ventricular internal dimensions. It is likely that right ventricular dilation indicates abnormal volume/pressure relationships of the right heart and that this abnormality, through alterations in venous and lymphatic drainage, underlies the accumulation of pericardial effusion in these patients with heart disease with or without congestive heart failure.
Kaposi sarcoma, a common opportunistic neoplasm complicating AIDS, is thought to arise from the vasculature and possibly from lymphatic endothelium. To evaluate the nature and extent of lymphatic involvement in AIDS-associated Kaposi sarcoma, we used an improved technique of whole-body lymphangioscintigraphy. Six human-immunodeficiency-virus-seropositive men (40-51 years old) with AIDS and extensive Kaposi sarcoma had bilateral foot and/or hand intradermal injection of 0.05 ml of 99mTc-labeled human serum albumin (500 microCi, 18.5 MBq). After sequential whole-body scanning with a digital gamma camera, the findings were interpreted by comparing them with findings from similar studies in 30 other patients without AIDS or Kaposi sarcoma (26 with primary or secondary lymphedema and four with normal extremities). Unlike in normal limbs, where lymphangioscintigraphy displayed early lymphatic truncal and regional nodal filling with radionuclide, in patients with Kaposi sarcoma, lymphangioscintigraphy disclosed a variety of abnormal patterns with some features distinct and others resembling lymphatic dysplasia as seen in primary and secondary lymphedema. These included focal accumulation of tracer within lymphatic channels in the distribution of cutaneous Kaposi lesions; delayed tracer transport with absent, faint, or intense regional lymph nodal uptake; and retarded or impeded lymphatic drainage with tracer intensification in the region of Kaposi sarcoma plaques. The impaired lymphatic drainage and nodal dysfunction seen on scintigrams in patients with AIDS-associated Kaposi sarcoma suggest a close connection between the lymphatic system and this disorder.
OBJECTIVE: To improve the diagnosis and treatment of pulmonary lymphangioleiomyomatosis (PLAM). METHODS: Three patients with PLAM confirmed by pathological assessment were presented and relevant literatures were reviewed. RESULTS: PLAM is a rare pulmonary disease of unknown cause. The clinical manifestations were pneumothorax, exertional dyspnea and hemoptysis. Pulmonary function test showed obstructive or compound ventilative defect and hypoxemia. HRCT showed bilateral diffuse cystic airspaces change. Pathological features showed abnormal smooth muscle proliferation occurred along lymphatics. Lymphatics dilated and proliferated. CONCLUSIONS: The prognosis of PLAM is poor. There is no effective method for the treatment of this disease at present.
Histologically, lymphangiomatosis is a rare type of benign neoplasm caused by abnormal development and proliferation of the lymphatic system. Thoracic lymphangiomatosis can present in a localized (lymphangioma) or diffuse form (lymphangiomatosis). In most cases the disease progresses to serious morbidity or even death. The treatment of choice for localized disease is usually surgery or, less frequently, local injection of sclerosing agents (streptococcus antigen OK-432). However, in diffuse forms there is a gelatinous infiltrate without defined limits. In these cases the main treatment option is radiotherapy. We report 2 cases of diffuse thoracic lymphangiomatosis with pulmonary infiltrate. In both cases radiotherapy in appropriate doses successfully eliminated pulmonary infiltrates, pleural effusion, dyspnea, and general discomfort. Surgery was needed to resolve complications of the disease and for diagnosis.
After a brief review of the classical methodology and results of lymphoscintigraphy, the technique is considered in terms of an original kinetic study approach. Immediately after distal subcutaneous injection of a technetium colloid (rhenium sulfocolloid), 40 1-min serial images of the limbs are recorded followed 4 h after injection by recording of static images. The main abnormalities detected by scintigraphy concern the lymphatic vessels, nodes and interstitium. They reveal the presence of lymphedema and provide information about its mechanism, indicating, particularly in the case of primary lymphedema, whether there is predominant hyperplasia or hypoplasia in vessels or nodes. Synoptic study of the initial dynamic recording based on simple examination of serial images is difficult. Complementary data provided by activity curves determined from manually selected regions of interest (ROI'S) are of limited value since the ROI'S correspond to superimposed spatial structures. Two data-processing techniques--the condensed image (CI) and factorial analysis (FA)--were therefore applied to dynamic scintigraphic recordings in order to study lymphatic progress of the radiotracer in the legs. A complete dynamic series is described in two IC, one for each leg. The CI, obtained by mounting the 40 serial images in vertical strips 1 pixel in width, describes the spatial distribution of radioactivity along the leg during recording. Factorial analysis provides automatic extraction of pure kinetic components or factors from the dynamic series despite their spatial superposition. The factors are described by factorial curves and factorial images representing the spatial identity of the factor. Three-factor FA was applied successively to each leg.(ABSTRACT TRUNCATED AT 250 WORDS)
Wrist arthrography can be helpful in the evaluation of the chronically painful wrist and, more specifically, in visualization of the integrity of the triangular fibrocartilage and interosseous ligaments. To be meaningful, arthrographic findings, i.e., compartment communication, synovial irregularity, tendon sheath and lymphatic visualization, loose bodies, and cartilage abnormalities, must be correlated with clinical history and physical examination.
Lymphangioleiomyomatosis (LAM) is defined as an abnormal proliferation of smooth muscles around lymphatics, venules, and brochioles. This article describes our experiences treating a 21-year-old, white female who experienced recurrent shortness of breath during air travel last year. Her episode was severe and the patient was transported to the hospital as soon as the airplane landed. Physical exam in the emergency room was significant for absent breath sounds on the right side and the chest X-ray revealed a pneumothorax. She required two chest tubes for complete lung re-expansion. Further evaluation showed an obstructive pattern and air trapping on pulmonary function tests. This patient was treated with Medroxyprogesterone acetate (MPA) for six months and subsequent pulmonary function tests revealed improvement in her condition.
S-1, an antineoplastic formulation of a fluorinated pyrimidine derivative containing tegafur (FT), CDHP, and potassium oxonate (Oxo) in a molar ratio of 1:0.4:1, was recently developed by Taiho Pharmaceutical Co., Ltd., with the aim of prolonging the effective plasma concentration of 5-fluorouracil (5-FU) over that produced by FT alone and reducing its dose-limiting gastrointestinal toxicity. As a part of the S-1 toxicity study, the single-dose toxicity of S-1 as well as that of its components, CDHP and Oxo, was investigated in mice, rats, and dogs. The following results were obtained. 1. In mice and rats, excretion of diarrheal stools, salivation, and alopecia were observed after S-1 administration. In severe cases, the animals subsequently showed emaciation due to weight loss or suppressed weight gain, decreased spontaneous motor activity, an anemic appearance, bradypnea, prone position, and death. In the CDHP and Oxo treatment groups of rats, the only toxic signs were soft or diarrheal stools on the dosing day. 2. In dogs, vomiting and excretion of diarrheal, mucous, or soft stools was observed after S-1 administration. In the CDHP and Oxo treatment groups, excretion of soft and diarrheal stools and vomiting were observed relatively frequently from the dosing day until day 1. 3. In the pathological examination of the animals given S-1, mice and rats showed pulmonary congestion/edema, dark red discoloration of the mesenteric lymph nodes, atrophy of lymphatic tissues such as the thymus and lymph nodes, decreases of lymphocytes in the splenic white pulp and mesenteric lymph nodes, a decrease in bone marrow cells, congestion of the glandular stomach, and aggregates of bacteria in the lung, liver, or spleen. In dogs, abnormal changes were observed mainly in the lymphatic organs such as the thymus and lymph nodes. 4. The LD50 values of S-1 in terms of the amount FT they contained were estimated to be 549 mg/kg for mice(male), 441-551 mg/kg for rats (both sexes) and about 53 mg/kg for dogs (male). The LD50 values of CDHP and Oxo were 2000 mg/kg or higher for both rats (both sexes) and dogs (male). 5. Hematopoietic and lymphatic impairments, immunosuppression associated with respiratory were considered to be the cause of death from S-1. The toxicity of S-1 reflects the toxicity of 5-FU and was not found the different toxicity by the addition of CDHP and Oxo.
The process and route of bacterial translocation from the gut after major liver resection remain unclear. In the present study enteric bacterial translocation, enterocyte ultrastructure in the ileum and colon, the process and route of bacterial invasion and the permeability of the cell membrane system and blood-tissue barrier were evaluated in rats receiving sham operation, and 70 or 90 per cent hepatectomy. The incidence of bacterial translocation to mesenteric lymph nodes was 80-100 per cent in rats 6 h after 70 per cent and 2-4 h after 90 per cent hepatectomy, and 80-100 per cent to the systemic circulation 2-4 h after 90 per cent hepatectomy but only 20 per cent to the portal vein. An increase in bacterial adherence to the intestinal surface, damage to the permeability of the cell membrane system and blood-tissue barrier, and pathological alterations in the ileum and colon developed, correlating with the extent of liver removed and the time that had passed after hepatectomy. Most translocating bacteria appeared in morphologically intact enterocytes with increased membrane permeability, in antigen-presenting cells and in submucosal lymphatics, but some bacteria were also seen within damaged enterocytes 4h after 90 per cent hepatectomy. These results indicate that altered permeability of the cell membrane system may be one of the earliest characteristics of challenged enterocytes, and that enteric bacteria translocate through both morphologically normal and abnormal enterocytes. Translocation occurred mainly into the lymphatics, bacteria either being 'carried' by antigen-presenting cells or entering by active invasion.
The past 15 years have witnessed an explosion of knowledge about blood vascular endothelium due in large part to in vitro growth of endothelial cells from both large blood vessels and capillaries. In contrast, little comparable information has accumulated on endothelium of lymphatics, which lie in intimate contact with parenchymal cells and drain excess fluid, macromolecules, particles, and immunocompetent cells in a continuous recirculation between tissues and bloodstream. While structural and functional differences between the two vascular systems have been described in vivo, in tissue sections, and in isolated preparations, similarities are notable in ultra-structure, biochemistry, physiology, and pharmacologic responsiveness, and these may predominate under pathologic conditions. In 1984, three separate groups described in vitro culture of lymphatic endothelial cells from collecting ducts and cavernous lymphangiomas. Lymphatic, like blood vascular, endothelium grows in confluent monolayers, "sprouts", synthesizes Factor VIII-associated antigen and fibronectin, and ultrastructurally shows Weibel-Palade bodies; overlapping intercellular junctions and anchoring filaments typical of lymphatic endothelium are also found. Genetic, congenital, and acquired disorders such as strangulating fetal nuchal cystic hygromas (Down and Turner syndromes), vascular tumors and dysmorphogenesis (Maffucci and Klippel-Trenaunay syndromes), Kaposi's sarcoma, lymphogenous and hematogenous spread of cancer, and parasitic infestations such as filariasis, share overlapping abnormalities in formation, growth, and/or neoplasia of lymphatics and blood vessels. In these and similar clinical disorders, confusion often exists as to the nature of the cell or tissue of origin, and insight into the role and control of hemangiogenesis and lymphangiogenesis is still in its infancy. Nonetheless, with the ever widening array of investigative techniques, it is not only timely but imperative to explore the endothelial biology underlying these inborn and acquired disorders.
PURPOSE: Although it has been suggested that cathepsin D, a lysosomal protease, is involved in tumor invasion and metastasis in human colorectal cancers, conflicting studies have also been reported recently. In addition, this issue has been only rarely studied in human colorectal tumors by use of immunohistochemical methods. The aim of the study presented here was to clarify not only the correlation between cathepsin D expression and tumor invasion or metastasis but also the correlation between the intracellular immunostaining pattern of cathepsin D and tumor invasion and metastasis in human colorectal tumors. METHODS: Thirty-four primary colorectal adenocarcinomas and 24 adenomas were immunostained by use of an anticathepsin D antibody. Both the incidence and the immunostaining patterns of cathepsin D were investigated in all tissue samples. RESULTS: Three different immunostaining patterns, i.e., supranuclear, basal, and diffuse, were observed in samples containing cathepsin D. Although the incidence of cathepsin D-positive carcinomas was not correlated with tumor progression, invasion, or metastasis, the immunostaining pattern was significantly correlated with lymphatic invasion. CONCLUSIONS: The results of this study suggest that abnormal cathepsin D immunostaining patterns (basal or diffuse) can be used to predict a potential for lymphatic invasion in colorectal carcinoma.
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Bilateral lethal chylothoraces developed in a premature infant secondary to superior vena caval obstruction related to central venous catheterization for total parenteral nutrition. The accumulation of chyle in the lungs was preceded radiographically by the typical lymphatic pattern in the lungs, usually associated with lymphangiectasia. A nuclear medicine lymphangiogram showed abnormal accumulation of the isotope in the lungs secondary to the lymphatic obstruction.