Lymphatic Interruption Research Articles

Diffuse Large B Cell Lymphoma, Bilateral Lower Extremity Lymphedema, and Ulcerated Inguinal Lymph Node

Lymphedema (LE) is a chronic medical condition characterized by lymphatic fluid retention, resulting in tissue swelling. There are two general classifications of LE; primary and secondary which are based on two mechanisms; lymphatic obstruction and lymphatic interruption. The most common cause of LE in the developing world is secondary to an infection known as filariasis. Cancer including Hodgkin and non-Hodgkin lymphomas; and its treatment are some causes of secondary LE. LE also could maintain the persistence of an occult localization of lymphoma. This case illustration describes a female, 57 year-old with stage II lymphedema of both legs, bilateral inguinal lymphadenopathies that were biopsied. The filarial blood examination was negative. Biopsies showed diffuse large B-cell lymphoma.

Chylous Ascites after Laparoscopic Retroperitoneal Lymph Node Dissection for Ovarian Cancer: A Case Report and a Review of Literature

Study Objective: Chylous ascites, a rare entity, is a documented complication of surgical dissection in the retroperitoneal space due to interruption of lymphatics. More cases of postoperative chylous ascites are being reported in the gynecologic literature. We report a case of postoperative chylous ascites and review the literature.

Fluid Management of Patients Undergoing Intestinal and Multivisceral Transplantation

Small bowel transplantation can be associated with large fluid shifts due to massive blood loss, dehydration, vascular clamping, long ischemia times, intraoperative visceral exposure, intestinal denervation, ischemic damage, and lymphatic interruption. Fluid management is the major intra- and postoperative problem after small bowel and multiple organ transplantation, because of the highly variable fluid and electrolyte needs of the transplant recipient. Third-space fluid requirements can be massive; inadequate replacement leads to end-organ dysfunction, particularly renal failure. Several liters of fluid may be required in the initial 24 to 48 hours postoperatively to simply maintain an adequate central pressure to provide a satisfactory urine output. During this time patients may develop extensive peripheral edema, which dissipates over the next few days as the fluids are mobilized and requirements stabilize. Based on our experience in 29 cases of intestinal transplantation and 4 cases of multivisceral transplantation, we have herein described the intraoperative fluid management and hemodynamic changes. Our study confirmed a large quantity of fluid administration during and after small bowel transplantation that required adequate volume monitoring.

Cardiac Lymphatic Interruption is a Major Cause for Allograft Failure after Cardiac Transplantation

Cardiac transplantation is one of the most effective treatments of end stage heart failure to date, although it comes with risks. One of the major complications of cardiac transplantation is allograft failure, which is caused by ischemic injuries, pulmonary hypertension and chronic rejection. Recent animal and human studies have demonstrated that cardiac lymphatic obstruction leads to significant myocardial fibrosis and depression in contractile forces. We hypothesize that lymphatic interruption, which is almost inevitable after cardiac transplantation, is a major cause of cardiac allograft failure through direct damages to the myocardium and also through the formation of allograft coronary vasculopathy.

Octreotide in the treatment of small intestinal dysfunction after a model of jejunoileal autotransplantation in the pig.

Enteric denervation and ischemic injury contribute to dysmotility and malabsorption following intestinal transplantation. We hypothesized that, by prolonging bowel transit and by ameliorating dysmotility, octreotide (OT) may improve cholesterol and bile acid absorption after jejunoileal autotransplantation. Seventeen pigs with fixed food intake underwent either jejunal transection (n = 6), or jejunoileal autotransplantation, which includes extrinsic autonomic denervation, lymphatic interruption, and in situ cold ischemia (n = 11). Five randomly chosen autotransplanted animals received intramuscular long-acting OT (10 mg) once a month. After 8 weeks, weight gain, intestinal transit time, fecal excretion of bile acids and cholesterol, and fractional cholesterol absorption were determined. Jejunal and ileal specimens were collected for histochemical analyses. Plasma cholestenol and campesterol, respective markers of cholesterol synthesis and absorption, were measured after 2 and 8 weeks. Following jejunoileal autotransplantation, octreotide treatment significantly increased the median intestinal transit time from 22.8 to 24.8 h and the median body weight gain from 166 to 187%. Jejunoileal autotransplantation significantly increased fecal bile acid excretion, plasma cholestenol, and bacterially modified fecal neutral sterols, and decreased absorption of cholesterol, plasma campesterol, and biliary cholesterol secretion. These changes were not significantly modified by OT treatment. Bowel wall and mucosal structure, mucosal proliferation, and weight or microvilli showed no statistically significant differences between autotransplanted animals with or without OT treatment. Findings of the present study suggest that octreotide prolongs intestinal transit time and improves weight gain after jejunoileal autotransplantation, but has no effect on malabsorption of cholesterol and bile acids.

Growth hormone selectively improves intestinal cholesterol absorption after jejunoileal autotransplantation in pigs

Background/Purpose Small bowel transplantation impairs enteric function and causes malabsorption of cholesterol and bile acids. Growth hormone stimulates intestinal absorptive function. The authors hypothesized that long-term growth hormone therapy could improve absorption of bile acids and cholesterol after autotransplantation of the jejunoileum. Methods Sixteen pigs with similar food, cholesterol, and fat intake underwent either sham laparotomy or a model of jejunoileal autotransplantation, including extrinsic autonomic denervation, lymphatic interruption, and in situ cold ischemia. Five randomly chosen autotransplanted animals received daily growth hormone treatment for 8 weeks. Serum lipids, absorption, and excretion of cholesterol, bile acids, and fat were determined after 8 weeks. Mucosal morphometrics, proliferation, and enzyme activities were determined. Plasma cholesterol precursors and plant sterols, respective markers of cholesterol synthesis and absorption, were measured after 2 and 8 weeks. Results After jejunoileal autotransplantation, growth hormone treatment significantly increased body weight gain, cholesterol absorption efficiency from 45.1% to 62.1%, plasma campesterol to cholesterol proportions, and biliary secretion of cholesterol. With or without growth hormone treatment, autotransplantation significantly increased fecal bile acid excretion, plasma cholesterol precursors, fecal bacterially modified neutral sterols, mucosal thickness of the ileum (but not jejunum), and intestinal transit time when compared with sham-operated animals. Crypt cell proliferation, mucosal enzyme activities, and microvilli showed no differences between the groups. Conclusions These findings suggest that growth hormone treatment selectively improves cholesterol, but not bile acid absorption, after autotransplantation of the jejunoileum.

The pathomechanism of posttraumatic edema of lower limbs: I. The effect of extravasated blood, bone marrow cells, and bacterial colonization on tissues, lymphatics, and lymph nodes.

The mechanical injury of soft tissues and bones of lower extremities is frequently followed by long-lasting edema at the site of trauma and distally. The pathomechanism of this complication remains unclear. Venous thrombosis and interruption of lymphatics are considered to be the main etiologic factors. We propose a concept that protracted healing of injured tissues and bones with involvement of the regional lymphatic system (lymphatics and nodes) is responsible for persistence of edema. The events affecting the first (scavenging) phase of healing of traumatized tissues, such as hematoma, translocation of bone marrow cells to soft tissues, and colonization by microorganisms, and in particular their effects on lymphatics and lymph nodes, were studied. Mongrel dogs weighing 15-20 kg were used. Fresh blood or bone marrow cell (BMC) suspension was injected subcutaneously or intralymphatically into the paw. Strains of saprophyte bacteria residing on the skin surface were cultured and injected intradermally. Oil-contrast lymphography was performed before and after injections to evaluate the changes in lymphatics and nodes. Biopsy samples of paw skin, subcutaneous tissue, and regional lymph nodes (LN) were taken. The responsiveness of LN lymphocytes was studied in autologous mixed cultures with peripheral blood lymphocytes (PBL), BMC, and cultured bacteria. The PBL from subcutaneously injected blood were evacuated by the lymphatic route at a rate of 1-3%/6 hr. There was no thrombosis of lymphatic vessels or obstruction of LN sinusoids. The BMC evoked major inflammatory changes in both the skin and the LN. Bacteria caused local inflammation, dilatation of lymphatics, and destruction of node parenchyma. Autologous BMC and PBL stimulated LN lymphocytes in a 6-day culture. The responsiveness of lymph node lymphocytes to previously subcutaneously injected bacterial antigens was increased. The extravasated blood did not produce changes in skin, subcutaneous tissue, and lymphatics; however, it stimulated LN lymphocytes. The BMC and saprophyte bacteria caused major local and lymph node inflammatory response. All these factors may contribute to the local edema in the initial phases of healing of traumatized tissues.

Sentinel node study in early breast cancer.

Since October 1997 60 patients with early breast cancer (T <3 cm) were studied. All patients underwent lymphoscintigraphy with two types of colloid: the first (17 pts) with a particle size <1,000 nm; the second (43 pts) with a particle size <80 nm. The standard procedure consists of injection, on the day before surgery, of 70 MBq of the smaller nanocolloid in 0.4 cc saline divided over four sites, around the lesion or subdermally around the surgical scar. We utilize a low-energy, high-resolution LFOV camera for scintigraphy and a probe specific for the sentinel node during surgery. In 56/60 patients (93.3%) lymphoscintigraphy showed the sentinel node (SN). In two cases the SN was not detected presumably because of lymphatic interruption by an old surgical scar; in the other two cases the sites of injection were too close to the SN, thus masking it. In five cases (9%) the SN was not visualized with the surgical probe but in two of these drainage to the internal mammary chain was observed. The apparently lower sensitivity of intraoperative localization was due to the extra-axillary lymphatic drainage or to the vicinity of the SN to the primary lesion. The SN proved to be metastatic in 12 cases. No false-negative SNs were found. In five cases (10%) the radiolabeled lymph node was the only node containing tumor cells (micrometastases): this result depends on the combined use of hematoxylin-eosin and rapid cytokeratin staining. The application of blue dye was useful for easier identification of the SN but did not allow detection of more SNs. Our preliminary results are extremely encouraging. Considering that at the early stages of breast cancer the likelihood of lymph node metastases is low (20% in our series) and no false negative were reported in this study, we conclude that with SN biopsy axillary lymph node dissection can be avoided, making surgery less aggressive but maintaining accuracy.

Fecal fat, cyclosporine, and α1-antitrypsin for assessment of small bowel function following transplantation

Many factors affect the integrity of transplanted small bowel. These include ischemic preservation and immunologic injury as well as the division of intestinal lymphatics during transplantation. This study was undertaken to evaluate the recovery of fat absorption in transplanted small bowel in syngeneic rats. Orthotopic transplantation of the total small bowel with resection of the native intestine was performed. The experimental (n = 11) and a pair-fed, shamoperated control (n = 8) groups were fed a 50% kcal corn oil semipurified diet. Studies of cyclosporine (CSA) absorption, maltose absorption, dietary fat, and fecal α 1-antitrypsin (FA1AT) excretion in transplanted animals were performed preoperatively and at 15, 30, and 50 days postoperatively. There was no significant difference in the weight change or fat and maltose absorption in experimental animals compared with control animals at any time point. Peak serum CSA levels were lower at day 15 in transplanted animals than in controls ( P = 0.006) and improved but remained lower than those in controls at days 30 and 50 ( P = 0.017). FA1AT excretion was increased on postoperative day 15 (accompanied by a decrease in body weight) and returned to control levels at days 30 and 50. Transplanted isogeneic rats had weight recovery and fat and carbohydrate absorption similar to those of controls. Transplanted animals had a protein-losing enteropathy measured by FA1AT at day 15 that resolved by 30 and 50 days, respectively. CSA absorption showed a much more gradual return to control levels and remained abnormal at 50 days. These data suggest that there is transient interruption of intestinal lymphatics after transplantation, but overall recovery and fat absorption are surprisingly unaffected in this model.

Chest radiographic findings after bilateral lung transplantation

We reviewed the postoperative chest radiographic and CT findings in the first 13 patients who underwent bilateral lung transplantation at our institution. Portable chest radiography was performed daily for about 10 days, after which upright posteroanterior studies were performed daily for about 10 days, and then as clinically required. CT was performed when a complication was suspected. The reimplantation response (noncardiogenic pulmonary edema due to ischemia, trauma, denervation, and lymphatic interruption) occurred in 12 patients and usually consisted of bilateral perihilar and basal consolidation. Twelve episodes of acute rejection, an imprecise clinical diagnosis, occurred in 10 patients. Radiographic changes consisted of bibasal (n = 2), right mid and lower (n = 2), or left basal consolidation (n = 1); there were no changes in seven episodes. Radiographic resolution occurred in four cases after administration of IV steroids. The radiographic findings associated with the reimplantation response and rejection were nonspecific and were mimicked by fluid overload and infection. Bronchial dehiscence and/or stricture formation occurred in seven patients; generally chest radiography was inaccurate and CT was very accurate in the assessment of these complications. Chest radiography was helpful but not definitive in sorting out the problems occurring in the postoperative period after bilateral lung transplantation. CT was excellent for use in demonstrating airway problems.

Functional Characteristics of Veiled Cells from Canine Prenodal Lymph

The surgical interruption of afferent lymphatics in the hind limb of dog leads to peripheral lymph stasis. The stagnated lymph contains large numbers of immunocompetent cells originating solely from the skin. This experimental model allows a study of the functions of the afferent skin-draining lymph cell population, the recovery and assessment of the lymphokines and other mediators liberated by these cells during the culture, and the production of anti-sera against different types of lymph cells. In the present study, we focused on the functional, morphological and cytochemical evaluation of the non-lymphoid cells, isolated from the whole lymph cell population by means of the gradient centrifugation technique. The non-lymphoid cells were large, with an irregularly- shaped nucleus and numerous cytoplasmic projections, giving them a «eiled» cell (VC) appearance. All VC were strongly positive for DLA-class II antigens and membrane-associated ATP-ase, and 60% of them exhibited the activity of non-specific esterase. In the functional assays, VC displayed the potent accessory-cell activity in the mitogen-induced response of autologous blood- and lymph-derived lymphocytes. In the mixed leukocyte cultures, VC acted as stimulators of the allogeneic and autologous lymphocyte proliferation. The high spontaneous and mitogen-induced responsiveness of the whole lymph cell population was found to be dependent on the presence of VC. The small number of VC (5% of cultured cells) was sufficient to produce the above-mentioned effects. These results indicate that VC is a cell responsible for the antigen presentation in the skin-associated immune reactions in dog, which is relevant to the observations on similar cells from the other species.

Heart-lung transplantation: the postoperative chest radiograph.

The postoperative chest radiographs of 10 patients who had undergone heart-lung transplantation at Stanford University Medical Center were evaluated and compared with those of 10 consecutive cardiac transplantation patients and 10 consecutive coronary artery bypass graft patients. In the second week after surgery, we observed an interstitial radiographic pattern in the heart-lung transplantation patients but not in the other two patient populations. This pattern, which did not correspond with any clinical evidence of infection, rejection, fluid overload, or oxygen toxicity, may represent the reimplantation response described in dogs and primates following transplantation of a single lung. This response may be related to the interruption of bronchial circulation, the denervation of both lungs, and the lymphatic interruption that occur during transplantation. It may also be related to the obligatory period of ischemia that is incurred during implantation.

Hemodynamic pulmonary edema in dog lungs after contralateral pneumonectomy and mediastinal lymphatic interruption.

The effect of pneumonectomy and mediastinal lymphatic interruption on gravimetrically measured extravascular lung water was studied in dogs. Raising left atrial pressure to 23 mm Hg caused a significant increase in extravascular lung water in normal dogs compared to controls. The same hemodynamic challenge, however, when applied to pneumonectomized dogs caused a significantly greater increase in extravascular lung water than in the hemodynamically challenged normal dogs. When a moderate mediastinal lymphatic interruption was added to the pneumonectomy, there was no additional increase in extravascular lung water. We suggest that the remaining lungs after contralateral pneumonectomy are more prone to extravascular fluid development when subjected to a significant hemodynamic challenge because of the combination of an increase in transmembrane fluid transudation into the interstitium of the remaining lung and loss of parenchymal/hilar lymphatic drainage routes. In this situation, lymphatic clearance thresholds are more easily exceeded, extravascular fluid accumulates and pulmonary edema is the result.

Femoro-popliteal bypass simplified.

There is increasing emphasis on carrying femoro-popliteal bypass grafts below the knee and most vascular surgeons agree that reversed saphenous vein makes the best graft. However, some other considerations have become important and deserve consideration. P.T.F.E. grafts in this location have almost as good a long term patency rate as autologous vein grafts. Some very experienced vascular surgeons have indicated their preference for this type of graft, citing some of these pertinent reasons: Peripheral vascular disease usually is associated with lesions in other vessels. Since coronary artery bypass has become so commonly used to stave off myocardial infarction some thought should be given to preservation of suitable saphenous veins for this purpose. Harvesting the saphenous vein adds additional surgical trauma, time, exposure to sepsis, lymphatic interruption and extra incisions. Once we opt for preferential P.T.F.E. grafts, then we start to search for a simpler technique.

The role of the regional lymph node in the response to secondarily vascularized grafts.

Studies using neonatal hearts grafted into the foot pads of adult rats have shown significant differences in the tempo of rejection in various RT1-incompatible combinations of donor and recipient rats. The model allows simultaneous study of events in the graft and in the regional node draining the graft. Removal of the regional node in the inductive stages of the immune response resulted in highly significant prolongation of graft survival. This effect was not due to lymphatic interruption per se or to clonal deletion. The effect was independent of the presence of the primary graft. Second grafts implanted in animals from which both the original graft and its regional node had been removed showed prolonged survival. Once survival of the original graft, from which the node was removed, was established, survival of second grafts bearing the same antigens was also prolonged, although third-party grafts were rejected in first set time. The data suggest that the microenvironment and anatomical connections of the lymph node that first receives antigen, or the cells that have contacted antigen in the graft, or both, play a vital role in an orderly sequence of cellular interaction and migration that culminates in graft rejection. Interruption of this sequence by node removal appears to divert the alloimmune response toward specific enhancement of the graft.

"Radionuclidc Lymphography: A Demonstration of Surgical Lymphatic Interruption"

Department of Nuclear Medicine, Milwaukee Children's Hospital, 1700 West Wisconsin Avenue, Milwaukee, Wisconsin 53201

The effect of lymphatic interruption and immediate vascularization on the afferent arc of skin graft rejection.

Allografted skin is more rapidly rejected than other organs such as kidney and heart, and its survival is less easily prolonged by immunosuppressive agents or by immunologic enhancement (1). Many explanations for this phenomenon have been given: 1) the rate of vascularization has been suggested to be important in view of the fact that the vascularization of skin grafts is delayed for several days, whereas whole organ grafts are immediately vascularized. Delayed vascularization may result in ischemic damage with greater vulnerability to immunologic attack (2); 2) skin has a relatively rich lymphatic drainage system which is reestablished post-transplantation. Barker and Billingham (3) have demonstrated that the lymphatics are the prime source of sensitization in skin. Similar findings could not be demonstrated in kidney grafts (4); 3) evidence is also accumulating that there is a quantitative and/or qualitative difference in the antigenicity of skin and other organs (5); 4) whole organs evoke more of a humoral than cellular reaction than skin, and may be autoenhancing.KeywordsBrown NorwayVentral SkinImmunologic AttackVentral Abdominal WallSkin Graft RejectionThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Problems in absorption and immunosuppression after entire intestinal allotransplantation

Orthotopic entire small intestine allografts were transplanted in twenty dogs. Ten of these animals received immunosuppressive drugs. Allograft function was compared with that of other dogs subjected to complete intestinal denervation and lymphatic interruption. Dogs with denervated intestine showed decreased d-xylose absorption with reversal to normal rates within four months. Groups receiving allografts also showed depressed function which persisted for up to five weeks. Interestingly, dogs with untreated allografts showed no significant pathologic changes even though survival ranged from one to four weeks. In contrast, some dogs who received immunosuppressive drugs showed manifestations of organ rejection. Although we could not clearly demonstrate a graft versus host reaction in untreated allografts, it appears that entire small intestinal allografts, in the absence of these immunosuppressive drugs, can precipitate such a reaction. This phenomenon is believed to be related to the abundant lymphatic tissue found in the intestine.

Function studies after auto- and allotransplantation and denervation of pancreaticoduodenal segments in dogs

The functional and immunologic profiles of pancreaticoduodenal segments after auto- and allotransplantation or denervation were compared. Elevated serum amylase levels were seen immediately after surgery as a result of ischemic damage but statistically significant changes from the preoperative state did not occur. Hyperglycemia was not observed in allografted dogs until just prior to death. Rejection of pancreatic allografts was characterized by a late increase in serum amylase which was not observed in denervated or autografted dogs. Pancreatic denervation with lymphatic interruption or heterotopic autotransplantation resulted in only a temporary exocrine hypofunction whereas allotransplantation was associated with more permanent acinar damage. Islet cell function remained adequate in all groups. Pancreatic venous drainage directly into the systemic or portal systems did not significantly influence fasting blood glucose levels, although higher serum insulin levels resulted from pancreatic venous drainage into the systemic circulation.