Catecholamines in adrenergic nerve fibers of the lymph nodes after sympathectomy

Using Falck method in combination with microfluorimetry, catecholamine level in adrenergic nervous fibers has been measured in the canine popliteal lymph nodes, normal and in 12 h, 7, 30, and 90 days after unilateral lumbar sympathectomy. During first 24 h after the operation the level of catecholamines is for certain increased in the nervous fibers of the lymph node of the sympathectomized extremity. In 30 days after the sympathectomy their content drops at the side of the operation and increases in the contralateral extremity. By 3 months the equilibrium of the catecholamine content is restored in the nervous fibers of the lymph nodes in the homo- and contralateral extremities at the level higher than in the control. A conclusion is made that under conditions of unilateral sympathectomy only a partial sympathectomy of the popliteal lymph node is reached. All luminiscent adrenergic nervous fibers of the sympathectomized lymph node are processes of neurons, situating in the contralateral sympathetic trunk, or neurites of cells in sacral nodes, getting their preganglionic fibers from the contralateral trunk. The changes in catecholamine concentrations mentioned are considered as a compensatory reaction, directed to maintenance of general homeostatic equilibrium under conditions, when the nervous system transfers to a new level, ensuring the partly desympathized tissue by mediators.     

Lymphatic mapping and sentinel lymph node biopsy in patients with melanoma of the lower extremity

Lymphatic mapping and sentinel lymph node biopsy is a new technique used in the surgical treatment of patients with malignant melanoma. The purpose of this study was to evaluate the results of this approach for patients with melanoma of the lower extremity. Between May of 1994 and June of 1997 at the H. Lee Moffitt Cancer Center and Research Institute, 85 consecutive patients with clinical stage I and II melanoma of the lower extremity underwent lymphatic mapping and sentinel lymph node biopsy. These nodes were identified in all 85 patients by intraoperative lymphatic mapping with both radiolymphoscintigraphy and a vital blue dye injection. Eleven patients (12.9 percent) had histologically positive sentinel lymph nodes, and 10 patients underwent inguinal complete lymph node dissections. All 10 patients had no further histologically positive lymph nodes confirmed by subsequent complete dissection. Among 74 patients with histologically negative sentinel lymph nodes, only 2 patients (2.7 percent) developed inguinal nodal metastases during a mean follow-up period of 21.8 months (range, 13.5 to 58.3 months). The sensitivity of lymphatic mapping and sentinel lymph node biopsy in this series was 100 percent and the specificity was 97.3 percent. Therefore, we conclude that the use of lymphatic mapping and sentinel lymph node biopsy can accurately stage patients with melanoma of the lower extremity and provide a rational surgical approach for these patients.     

Avulsion injuries of the thumb

Avulsion amputations of the thumb are generally thought to have a worse prognosis after replantation than other amputations. We report the results of 17 thumbs that had an avulsion amputation and were replanted. Fourteen of the 17 survived (82 percent). Our experience indicated that the survival rate was improved by restoring continuity of at least two veins and two arteries, using a Y-shaped vein graft and the princeps pollicis artery for the source of arterial circulation. Nerve grafts were used to bridge defects in avulsed digital nerves. When possible, avulsed tendons were reattached to their muscle. Key pinch strength was 60 percent of normal, and grip strength was always less than that of the normal hand. The age of the patients and the cold ischemia time had no significant effect on either survival or function of the replanted thumb. When excellent venous backflow occurred immediately after the vessel repair and continued for at least 20 minutes, the thumb always survived without complications.     

Successful replantation in the face of absent venous drainage: an experimental study

Inadequate venous outflow is the factor most responsible in digital replantation failure and is a common cause of tissue loss in general. An experimental replantation model utilizing the rabbit ear was used to study the extreme example of venous congestion: absent venous drainage in the replanted part. Results of this study support the use of single arterial inflow along with an efferent AV fistula for outflow in the management of replants with absent venous drainage. Potential indications for the use of an efferent arteriovenous fistula in digital revascularization include the following: (1) the finding of distal veins too small to reanastomose, as is often the case in children and at distal levels in adults; (2) preferential destruction of distal venous structures, as commonly seen in degloving or other dorsal injuries; and (3) in the management of postreplant venous thrombosis.     

The ability of oxygenated fluorocarbon solution to minimize ischemic skeletal muscle injury

The amputated canine limb was used to create a devascularized skeletal-muscle-containing model. The extremity was perfused with one of several solutions or merely cooled as a preservative measure during the devascularized period and then replanted. Perfusion of the limb with oxygenated fluorocarbon solution minimized edema formation and leakage of skeletal muscle enzymes into the serum following revascularization as compared to the other perfusates or to mere cooling. Histopathologic changes within the revascularized muscle were also minimized by the oxygenated fluorocarbon perfusion. It is probable that these findings will correlate with improved function of replanted extremities or free muscle flaps. The applicability of these findings to human extremity replantation and free-flap transfer is postulated. However, long-term human studies will be necessary to assess the function of extremities and flaps perfused with this solution prior to its general use in extremity replantation and free-flap transfer.     

Replantation of fingertip amputation by using the pocket principle in adults

There are several treatment modalities for zone 1 or zone 2 fingertip amputations that cannot be replanted by using microsurgical techniques, such as delayed secondary healing, stump revision, skin graft, local flaps, distant flaps, and composite graft. Among these, composite graft of the amputated digit tip is the only possible means of achieving a full-length digit with a normal nail complex. The pocket principle can provide an extra blood supply for survival of the composite graft of the amputated finger by enlarging the area of vascular contact. The surgery was performed in two stages. The amputated digit was debrided, deepithelialized, and reattached to the proximal stump. The reattached finger was inserted into the abdominal pocket. About 3 weeks later, the finger was removed from the pocket and covered with a skin graft. We have consecutively replanted 29 fingers in 25 adult patients with fingertip amputations by using the pocket principle. All were complete amputations with crushing or avulsion injuries. Average age was 33.64 years, and men were predominant. The right hand, the dominant one, was more frequently injured, with the middle finger being the most commonly injured. Of the 29 fingers, 16 (55.2 percent) survived completely and 10 (34.5 percent) had partial necrosis less than one-quarter of the length of the amputated part. The results of the above 26 fingers were satisfactory from both functional and cosmetic aspects. Twenty of the 29 fingers, which had been followed up for more than 6 months (an average of 16 months), were included in a sensory evaluation. Fifteen of these 20 fingers (75 percent) were classified as "good" (static two-point discrimination of less than 8 mm and normal use). From the overall results and our experience, we suggest that the pocket principle is a safe and valuable method in replantation of zone 1 or zone 2 fingertip amputation, an alternative to microvascular replantation, even in adults.     

Limb preservation in replantation surgery

Five patients are presented in whom a traumatically amputated extremity or digit was perfused with oxygenated Fluosol DA-20%. Perfusion lasted between 16 and 46 hours. Microcirculatory oxygenation was monitored using pO2 measurements. Moreover, K?lactate, glucose, and ATP levels were measured and electron microscopic sections of the vessels were investigated at the end of the experiment. All above-mentioned parameters suggest that the tissue was sufficiently provided with oxygen and viable after many hours of perfusion. Conclusive evidence of the viability of a perfused digit was given by its successful replantation after 17 hours of Fluosol perfusion (at approximately 15 degrees C).     

Degree of chromatin activity and the RNA level in lymphocytes of popliteal lymph nodes of dogs after administration of an antigen]

In the experiment performed on 127 dogs by means of cytospectrofluorometric analysis, using fluorochrome acridine orange in dynamics up to 1 year, changes in the level of chromatin activation and RNA content have been studied in lymphocytes of the germinative centers and the crown of lymphoid nodules, in the paracortical zone and medullary cords of the regional and contralateral popliteal lymph nodes, after subcutaneous injection of antigen (BCG vaccine, 0.2 mg/kg) into the lateral area of the foot of the left pelvic extremity. The immune response is accompanied with a periodical increase in the level of chromatin activation and RNA content in populations of lymphocytes in the regional and contralateral popliteal lymph nodes with maximum in 6 h, 3-7 days, 1-3 months after the antigen injection. The intensity of these processes has an unequal level in lymphoid cells of various structural components; it is higher in lymphocytes of the contralateral lymph node.     

The use of arteriovenous anastomosis for replantation of the distal phalanx of the fingers.

Microvascular replantation at the distal phalangeal level has recently been reported by several authors, but as yet the rate of success has not been constant owing to the technical difficulties associated with small vessels. To solve this problem, over the last 4 years we have used arteriovenous anastomosis to reestablish either the arterial system or the venous drainage system in the 33 digits of our 23 patients. The results have been excellent, with a 91 percent success rate. Such results for replantation of the distal phalanx may be maintained and improved if a small venous graft with several branches is also utilized.     

Saving Amputated Digits: Current Status of Replantation of Fingers and Hands

Since the advent of microsurgery in the 1960''s it has become possible to sucessfully repair vessels as small as 0.5 mm in diameter, which makes the replantation of totally severed digits possible. Some centers have reported 50 to 60 percent survival of completely severed digits and up to 100 percent survival of amputated hands and of partially amputed but otherwise non-viable digits that were reattached. In view of this success, severed members should be considered as potentially replantable.The recommended indications for replantation are: (1) multiple digital amputations at or proximal to the proximal interphalangeal joint; (2) amputation of the thumb; (3) amputation of the wrist or hand; (4) partially attached digits that are non-viable without reattachment.The surviving replanted digits give functional improvement to the hand and prove cosmetically acceptable.     

Sentinel lymph node biopsy in the management of cutaneous head and neck melanoma

Sentinel lymph node biopsy has revolutionized the surgical management of primary malignant melanoma. Most series on sentinel lymph node mapping have concentrated on extremity and truncal melanomas. The head and neck region has a rich and unpredictable lymphatic system. The use of sentinel lymph node mapping in the management of head and neck melanoma is evaluated. The authors conducted a retrospective review of patients treated for clinical stage I and stage II malignant melanoma of the head and neck with dynamic lymphoscintigraphy and gamma probe-guided sentinel lymph node biopsy. One hundred thirty-two patients (99 male patients and 33 female patients) were identified. The primary melanoma sites were the scalp (n = 54), ear (n = 14), face (n = 37), and neck (n = 27). Primary tumor staging was as follows: T1, 11; T2, 38; T3, 39; and T4, 44. Dynamic lymphoscintigraphy visualized sentinel lymph nodes in 128 patients (97 percent). In 71 cases (55 percent), a single draining nodal basin was identified, and in 57 cases there were multiple draining nodal basins (two basins, 55; three basins, two). Sentinel lymph nodes were successfully identified in 176 of 186 nodal basins (95 percent). Positive sentinel lymph nodes were identified in 22 patients (17.6 percent). Sentinel lymph node positivity by tumor staging was as follows: T2, 10.8 percent; T3, 19.4 percent; and T4, 26.8 percent. Completion lymphadenectomy revealed residual disease in seven patients (33.3 percent). Sentinel lymph node mapping for head and neck melanoma can be performed with results comparable to those of other anatomical sites.     

The dynamics of morphofunctional changes in the microcirculation of the pelvic extremity after modeling the chief stages of its replantation]

Under study was the effect of autotransplantation in its "pure form" upon the morpho-functional reconstruction and structural mechanisms of adaptation of the blood and lymphatic links of the microcirculatory bed of extremities during early postoperation period up to 10 days. The pathophysiological state of the extremity sufficiently close to its autotransplantation was obtained by means of circular transection of soft tissues of the medial third of the femur together with the nerves and deep collecting lymphatic vessels. It was found that after modeling the main stages of replantation in the fascia and periosteum of the operated extremity there developed a spasm of the arteriolar link and dilatation of the venular and lymphatic links of the microcirculatory bed. The areas of leukocytic infiltration with the phenomena of diapedesis and microhemorrhages were revealed along the course of postcapillaries and venules in the paravasal connective tissue. The amount of functioning arteriole-venular anastomoses was increased. Against the background of pronounced oedema of soft tissues of the operated extremity the venous pressure increased and the rate of the capillary bloodflow in the skin and muscles decreased. The above changes tend to be reduced by the 10th day after modelling the main stages of replantation of the extremity.     

Functional recovery of fluid drainage precedes lymphangiogenesis in acute murine foreleg lymphedema

Secondary lymphedema in humans is a common consequence of axillary lymph node dissection (ALND) to treat breast cancer. It is commonly hypothesized that lymphatic growth is required to increase fluid drainage and ameliorate lymphedema. Although there is a pronounced alteration in the balance of interstitial forces regulating fluid transport that sustains the chronic form of lymphedema, it is presently unknown whether changes occur to the balance of interstitial forces during acute lymphedema that may play a role in the recovery of fluid drainage. Here, we compared the relative importance of lymphangiogenesis of lymphatic vessels and interstitial flows for restoring fluid drainage and resolving acute lymphedema in the mouse foreleg after ALND. We found that removal of the axillary lymph nodes reduced lymph drainage in the foreleg at days 0 and 5 postsurgery, with fluid tracer spreading interstitially through subcutaneous tissues. Interstitial fluid drainage returned to normal by day 10, whereas functional regrowth of lymphatic vessels was first detected by indocyanine green fluorescence lymphography at day 15, demonstrating that the recovery of interstitial fluid drainage preceded the regrowth of lymphatic vessels. This was confirmed by the administration of VEGF receptor-3-neutralizing antibodies, which completely blocks lymphatic regrowth. It was found that the recovery of interstitial fluid drainage and the natural resolution of acute lymphedema produced by ALND were not hindered by VEGF receptor-3 neutralization, demonstrating that interstitial fluid drainage recovery and the resolution of acute lymphedema are lymphangiogenesis independent. The data highlight the central role of the interstitial environment in adapting to lymphatic injury to increase fluid drainage.     

Dynamics of the functional activity of the lymph nodes under conditions of sympathectomy

By means of mechanotron 6MYIC and perfusion with physiological solution using the "running vesicle", dynamics of functional activity of the popliteal lymph nodes have been studied in 17 non-inbred dogs under conditions of unilateral sympathectomy for 1 week up to 5 months of the experiment. Dependence of the lymph node functional activity on the adrenomediator concentration level in their tissues has been determined by means of the microfluorometry method in the preparations treated after Falck-Hillarp method in E. M. Krokhina modification. Lymph nodes of intact dogs serve as a control. Unilateral sympathectomy of the lymph node is stated to produce an enhancement of the period for its filling and emptying with lymph, resulting from an increased level of the mediator in the fibrillar stroma at the expense of compensatory enhancement of functional activity of the nervous fibers of the contralateral origin. During the remote postoperative period the amplitude of the lymph node capsule fluctuations is stipulated by certain pathomorphological changes, produced by deficiency in concentration of catecholamines in the organ's parenchyma. As to the periodicity of the capsule fluctuations in the intact lymph nodes, it is limited with the cycle of 3-6 min.     

Simultaneous bilateral forearm revascularization

A successful simultaneous bilateral forearm revascularization was performed on a 17-year-old boy. Functional recovery of both forearms was evaluated 42 months after injury. The patient can use both hands for the activities of daily living. So far, he has been employed and has no significant psychological problems. Temporary intraluminal silicone shunts are extremely helpful for reducing ischemic damage to the injured limb. The sufficient skeletal shortening of the upper limb replantation is crucially important. The wounds must be managed by aggressive and repeated debridement. Accurate primary nerve repair is essential, and the early postoperative rehabilitation is also important to achieve a satisfactory functional return. The functional replanted or revascularized upper extremity is superior to an amputation or prosthesis, especially in the cases of bilateral upper extremity amputation or devascularization.     

Lymphatic Territories (Lymphosomes) in a Canine: An Animal Model for Investigation of Postoperative Lymphatic Alterations

Background

Lymph node dissection is often performed as a part of surgical treatment for breast cancer and malignant melanoma to prevent malignant cells from traveling via the lymphatic system. Currently little is known about postoperative lymphatic drainage pattern alterations. This knowledge may be useful for management of recurrent cancer and prevention of breast cancer related lymphedema. We mapped the complete superficial lymphatic system of a dog and used this canine model to perform preliminary studies of lymphatic architectural changes in postoperative condition.

Methods

Lymphatic territories (lymphosomes) were mapped with 4 female mongrel carcasses using an indocyanine green (ICG) fluorescent lymphography and a radiographic microinjection technique. Two live dogs were then subjected to unilateral lymph node dissection of lymph basins of the forelimb, and ICG lymphography and lymphangiogram were performed 6 months after the surgery to investigate lymphatic changes. Lymphatic patterns in the carcass were then compared with postoperative lymphatic patterns in the live dogs.

Results

Ten lymphosomes were identified, corresponding with ten lymphatic basins. Postoperative fluorescent lymphographic images and lymphangiograms in the live dogs revealed small caliber lymphatic network fulfilling gaps in the surgical area and collateral lymphatic vessels arising from the network connecting to lymph nodes in the contralateral and ipsilateral neck in one dog and the ipsilateral subclavicular vein in another dog.

Conclusion

Our canine lymphosome map allowed us to observe lymphatic collateral formations after lymph node dissection in live dogs. This canine model may help clarify our understanding of postoperative lymphatic changes in humans in future studies.     

The Vancouver Lymphadenopathy-AIDS Study: 3. Relation of HTLV-III seropositivity,immune status and lymphadenopathy.

In a study of 394 homosexual men recruited at the primary care level the prevalence of antibody to human T-lymphotropic retrovirus (HTLV-III) was higher among those with lymph node enlargement than among controls. The degree of abnormal immune function, as shown by abnormalities in immunoglobulin levels, immune complex activity and T-lymphocyte subsets, was correlated with the extent of lymphadenopathy. A similar pattern of immunologic abnormality was associated with seropositivity for HTLV-III antibody. However, HTLV-III seropositivity was the major determinant of immune function after adjustment for lymph node status. The results suggest that the immune dysfunction seen in patients with lymphadenopathy is due for the most part to the high prevalence of HTLV-III seropositivity in these populations. Lymphadenopathy, in many subjects, may in fact represent a physical sign of a stabilized compensated homeostatic host response. Factors responsible for severe immune decompensation associated with acquired immune deficiency syndrome (AIDS) may best be sought by prospective study of HTLV-III seropositive asymptomatic patients or those with stable persistent generalized lymphadenopathy and relatively normal immune function.     

The utility of sentinel lymph node biopsy in head and neck melanoma in the pediatric population

Intraoperative lymph node mapping and sentinel lymph node biopsy have proven beneficial techniques in staging adult patients with melanoma of the head and neck, where there is great variability in lymphatic drainage. This technique has also been applied to pediatric patients with truncal cutaneous melanomas in an effort to determine nodal status without the morbidity associated with complete lymph node dissection. Nevertheless, the utility of sentinel lymph node biopsy in head and neck melanoma in the pediatric population has not been established. The objective of the authors' study was to determine the clinical utility of intraoperative lymph node mapping and sentinel lymph node biopsy of head and neck melanoma in the pediatric population. The authors reviewed the records of seven pediatric patients with head and neck melanoma or borderline melanocytic proliferations of unknown biologic potential who underwent intraoperative lymph node mapping and sentinel lymph node biopsy between 1998 and 2001. All sentinel lymph node specimens were examined by a melanoma dermatopathologist for the presence of metastatic melanoma. The mean operative time for each case was 3 hours, 8 minutes (range, 2 hours, 15 minutes to 3 hours, 50 minutes). All seven pediatric patients who underwent extirpation of a primary head and neck melanoma and preoperative lymphoscintigraphy had unique and identifiable basins of drainage to regional nodal groups. Four of seven patients had at least one positive sentinel lymph node. Overall, five of 19 sentinel nodes (26 percent) resected had evidence of metastatic melanoma. Of the patients with positive sentinel lymph nodes, two of the primary lesions were diagnosed as melanoma while two were initially considered atypical melanocytic proliferations of uncertain biologic potential with melanoma in the differential diagnosis. Sentinel lymph nodes in pediatric patients with melanoma of the head and neck can be successfully mapped and biopsied, as in adult patients. In addition, this procedure can provide critical diagnostic information for those pediatric patients with diagnostically challenging, controversial, or borderline melanocytic lesions.     

The influence of afferent lymphatic vessel interruption on vascular addressin expression

Tissue-selective lymphocyte homing is directed in part by specialized vessels that define sites of lymphocyte exit from the blood. These vessels, the post capillary high endothelial venules (HEV), are found in organized lymphoid tissues, and at sites of chronic inflammation. Lymphocytes bearing specific receptors, called homing receptors, recognize and adhere to their putative ligands on high endothelial cells, the vascular addressins. After adhesion, lymphocytes enter organized lymphoid tissues by migrating through the endothelial cell wall. Cells and/or soluble factors arriving in lymph nodes by way of the afferent lymph supply have been implicated in the maintenance of HEV morphology and efficient lymphocyte homing. In the study reported here, we assessed the influence of afferent lymphatic vessel interruption on lymph node composition, organization of cellular elements; and on expression of vascular addressins. At 1 wk after occlusion of afferent lymphatic vessels, HEV became flat walled and expression of the peripheral lymph node addressin disappeared from the luminal aspect of most vessels, while being retained on the abluminal side. In addition, an HEV-specific differentiation marker, defined by mAb MECA-325, was undetectable at 7-d postocclusion. In vivo homing studies revealed that these modified vessels support minimal lymphocyte traffic from the blood. After occlusion, we observed dramatic changes in lymphocyte populations and at 7-d postsurgery, lymph nodes were populated predominantly by cells lacking the peripheral lymph node homing receptor LECAM-1. In addition, effects on nonlymphoid cells were observed: subcapsular sinus macrophages, defined by mAb MOMA-1, disappeared; and interdigitating dendritic cells, defined by mAb NLDC-145, were dramatically reduced. These data reveal that functioning afferent lymphatics are centrally involved in maintaining normal lymph node homeostasis.     

磁共振间质淋巴造影实验研究

目的:探讨间质MR淋巴造影对肢体淋巴水肿的诊断价值。方法:用改良的Danese手术方法在13只新西兰大白兔后肢一侧形成淋巴水肿模型,另一侧作为对照。在每只大白兔双侧后肢足背部趾蹼处注射0.2ml欧乃影,按摩注射部位30秒钟。分别于造影剂注射前后进行三维MR淋巴造影及延迟淋巴造影成像。结果:实验侧淋巴管阻塞早期为渗出性改变及淋巴管侧支开放,晚期出现淋巴管扩张、迂曲、皮肤逆流。引流远端淋巴结显影较对照侧明显延迟。对照侧欧乃影吸收迅速,引流区域各组淋巴结、淋巴管及胸导管显示清晰。结论:间质MR淋巴造影可以在解剖背景下很好地显示引流区域淋巴管、淋巴结的解剖形态、功能及其异常表现。