Cervical Lymphatics Research Articles

Pathways of fluid drainage from the brain--morphological aspects and immunological significance in rat and man.

There is firm physiological evidence for the lymphatic drainage of interstitial fluid and cerebrospinal fluid from the brains of rats, rabbits and cats. The object of this review, is to describe firstly the morphological aspects of lymphatic drainage pathways from the rat brain and secondly, to explore through scanning and transmission electron microscope techniques, the possibility of similar lymphatic drainage pathways in man. Interstitial and oedema fluid spreads diffusely through the white matter in the rat and appears to drain into the ventricular cerebrospinal fluid. In grey matter, however, tracers pass along perivascular spaces to the surface of the brain and into the cerebrospinal fluid. Paravascular compartments in the subarachnoid space follow the course of major arterial branches to the circle of Willis and thence along the ethmoidal arteries to the cribriform plate of the ethmoid bone. Particulate tracers, such as Indian ink, enter channels in the arachnoid beneath the olfactory bulbs and connect directly with nasal lymphatics through channels which pass through holes in the cribriform plate. Proteins and other solutes may also drain along other cranial nerves. Thus, there is a bulk flow pathway for interstitial and cerebrospinal fluid from the rat brain into cervical lymphatics. In man, it is probable that diffuse interstitial drainage of fluid from the white matter occurs in a similar way to that in the rat. Furthermore, the anatomical pathways exist by which bulk drainage of fluid could occur along perivascular spaces from the grey matter into perivascular spaces of the leptomeningeal arteries and thence into the cerebrospinal fluid (CSF).(ABSTRACT TRUNCATED AT 250 WORDS)

Postoperative radiation therapy for cervical lymph node metastases from an occult squamous cell carcinoma.

One hundred thirteen patients with cervical metastases from a squamous cell carcinoma and no evidence of the primary tumor were treated for cure by surgery and routine large-field postoperative irradiation. Patients were staged according to the 1987 American Joint Committee on Cancer (AJCC) classification. There were 24 N1, 54 N2, 29 N3, and 6 Nx lesions. One hundred four patients underwent cervical lymph node dissection and 9 had adenectomy. All patients received postoperative external beam therapy to the entire naso-oro-pharyngo-larynx and all cervical lymphatics. The overall nodal failure rate was 13.7%. Nodal failure was significantly correlated with N staging (P = .01) and with the number of histologically involved nodes (P = .05). NOdal failure was 21% when nodes were initially fixed versus 7.5% when they were not (P = .07) and 18% when there was extracapsular spread versus 4.3% when the capsule was intact (P = .11). Eleven patients (9.7%) developed a subsequent primary lesion. In 3 patients (2.6%), this primary was located in the previously irradiated area and, in 2 cases, under the anterior block of lateral fields. Metastases occurred in 18 patients (16%). The five-year overall survival rate was 38%. Survival was correlated with N staging (P less than .02), nodal fixation (P = .05), extracapsular spread (P = .01) and loosely with the number of histologically involved nodes (P = .08). On the contrary, histological differentiation did not influence the local control rate, nor the development of metastases or subsequent primary lesions. Large-field prophylactic radiation therapy appears to be effective in preventing the emergence of initially occult primary lesions. However, control of disease in the neck and survival remain disappointing in patients with advanced nodal disease, even after combined surgery and radiation therapy.

Does the lymph drainage from the head influence aqueous humour outflow and visual functions?

Effect of lymphoedema of the head on the central nervous system is known. Possible changes in intraocular pressure, tonogram, electroretinogram, visual functions and ophthalmologic state was studied in animal experiments and in patients following serious surgical impairment of the cervical lymph drainage. Lymph drainage from the orbit to the deep cervical lymphatics was established, while no ophthalmologic alteration was detected after surgery.

Role of cervical lymph nodes in the systemic humoral immune response to human serum albumin microinfused into rat cerebrospinal fluid

The humoral immune response to human serum albumin (HSA) microinfused into cerebrospinal fluid (CSF) has been measured in serum, cervical lymph nodes, and spleen of Sprague-Dawley rats. Conditions were designed to promote normal brain barrier function. Serum titers of anti-HSA antibodies, primarily IgG, increased over 10 days and then persisted for at least 10 weeks. A significant role for cervical lymphatics in the systemic response to CSF-administered HSA is suggested, based on results showing that (1) cervical lymph obstruction reduces serum titers of anti-HSA antibodies, and (2) total antibody production by combined superficial and deep cervical nodes, sampled 14 days post-immunization, exceeds that by the spleen.

A modification of the MacFee incisions for neck dissection.

The dissection of cervical lymphatics for cancer after radiotherapy imposes a special need to ensure good healing of skin flaps with good access and acceptable aesthetic results. Adaptability of incisions for extended surgery is also desirable. Although it is felt that the adoption of the basic MacFee incision pattern fulfils these criteria, the author has for years employed curved modifications of the two horizontal incision lines. This develops a waisted skin bridge which is freely mobile and gives better access to the deep structures. The technique is contrasted with other approaches and described in detail. It complies with the safe principle of join-free linear incisions and is practical for regular use.

Technique of right lymphatic duct cannulation for pulmonary lymph collection in an acute porcine model

The pig is an increasingly preferred model for biomedical research, including studies for pulmonary pathophysiology. However, in piglets, the technique for cannulating the right lymphatic duct, which is subject to more anatomical variations and technically more demanding than that in dogs, has not been described. Our technique evolved to enable this collection of porcine lung lymph in acute experiments. The lymphatic ampulla is cannulated via one of the cervical lymphatics. The right lymphatic duct is invariably dorsal to the cranial vena cava and classically leads to the lymphatic ampulla. Yet in 18% of our pigs, cannulation was difficult or not feasible because the lymphatic duct either drained directly into the cranial vena cava at a distance from the lymphatic ampulla, or into the axillary lymph node of the first rib or the caudal deep cervical lymph nodes. Gently squeezing back regurgitated blood in the lymphatic ampulla before tying the suture and frequently withdrawing lymph with a syringe when the flow is small enabled us to collect clear lymph, usually immediately after completing the cannulation. The rate of lymph flow varied widely (1.7 ± 0.6 ml/hr) and increased when the left atrial pressure was raised. The lymph protein was 2.8 ± 0.2 g% with lymph/plasma protein ratio at 0.55 ± 0.04. The anatomical variations encountered in our 34 dissections, as well as the technical maneuvers found to be useful in the successful cannulation and collection of the porcine lung lymph, are described in detail.

Extracapsular spread of carcinoma in cervical lymph nodes. Impact upon survival in patients with carcinoma of the supraglottic larynx.

The treatment results and histologic findings in the cervical lymphatics of 96 patients with squamous cell carcinoma of the supraglottic larynx were studied retrospectively. The clinical assessment of the extent of disease in the cervical lymphatics correlated poorly with histologic findings. Forty-one percent of patients judged to have no evidence of cervical metastases were found to have carcinoma in the cervical lymphatics. Twenty percent of patients judged clinically NO were found to have extracapsular spread of tumor. Patients were subdivided according to the histologic findings in the cervical lymphatics. Three-year no-evidence-of-disease (NED) follow-up was available on all patients. Patients with no tumor in cervical lymphatics had a 71% 3-year NED. By comparison, patients with cervical metastases confined to the lymph node were 79% NED. Patients with histologic evidence of extracapsular spread of tumor were 45% NED (P less than 0.05). The use of histologic findings in predicting prognosis and treatment planning is discussed.

Nasopharyngeal carcinoma. Brief review

Nasopharyngeal carcinoma has a well-defined geographic distribution, primarily affecting persons from southern China and Southeast Asia. Environmental factors are numerous and appear to have a secondary role, mainly in the promotion of the neoplastic process. Relationship with the Epstein-Barr virus is indicated by the identification of viral genome copies within the cells and by a persistent host antibody response with restricted specificity for nasopharyngeal malignancies. The World Health Organization has recently adopted a histologic classification categorized into three subtypes according to the degree of epithelial differentiation, keratinization, and stromal lymphocytic infiltration. The tumor expands locally to contiguous structures, spreads through the cervical lymphatics following the jugular chain, and eventually metastasizes to the skeleton and liver. Primary management consists of radiation therapy to cervicofacial fields and usually offers adequate palliation, with a five-year median survival of 67 percent for stage I and 17 percent for stage IV disease.

Cervical lymph node metastases. Incidence and implications of extracapsular carcinoma.

The incidence and prognostic significance of extracapsular spread (ECS) of tumor in cervical lymphatics was investigated. The surgical specimens from 349 patients treated for squamous cell carcinoma by radical neck dissection between 1978 and 1982 have been examined retrospectively. Follow-up data were available relative to recurrence rate, site of recurrence, and disease-free intervals. Fifty-nine percent of the patients with N1 cervical metastases had ECS. Patients were classified according to the histopathologic findings in the radical neck dissection specimens. The three groups identified were patients with normal nodes, patients with no ECS, and patients with ECS. The histopathologic evidence of ECS was associated with a statistically significant reduction in survival when compared with patients without ECS. The disease-free interval between treatment and the development of recurrent disease was shorter for patients with ECS than for patients with no ECS.

Neck Node Immunoactivity in Head and Neck Cancer

Current conventional treatment for head and neck cancer is a non-specific approach which erradicates not only disease-containing but non-disease containing tissue. It was unknown whether or not this is a desirable feature. The experiments described in this report were designed to evaluate the regional immunoreactivity of lymphocytes derived from human neck nodes in patients with head and neck cancer. The stem cell assay was used to evaluate tumor-lymphocyte interactions. The results demonstrate that there is an active regional immune system within the neck nodes. This regional immune system is capable of being immunomodulated with non-specific immune stimulants. These results support the need to further study the regional immune system of the cervical lymphatics and to further pursue tumor-specific treatment programs.

Carcinoma of the anterior tongue.

We have reviewed 126 patients with squamous cell carcinoma of the anterior tongue. Our experience suggests that carcinoma of the anterior tongue is a highly aggressive disease. It is no less aggressive and dangerous than carcinoma of the posterior tongue. The clinically negative neck is a problem. Many clinical stage I and II cancers are, in fact, stage III when analyzed by the pathologist. This difficulty in clinical staging results in a significant management problem when stage III carcinomas are treated as stage I and stage II disease. Management, if it is to cure, must be aggressive. An adequate, wide surgical resection will control early carcinoma of the anterior tongue. Advanced cancers of the anterior tongue, clinical stages III and IV, should be widely excised; the cervical lymph nodes on the side of the primary lesion must be treated by surgery and radiation therapy. Treatment of the opposite side of the neck is indicated based on a high rate of metastases to contralateral lymph nodes in this series. Those patients treated with irradiation who had recurrence did so predominantly at the primary site of disease. Patients treated surgically tended to have recurrence in the regional cervical lymphatics.

Papillary Adenocarcinoma in Ectopic Thyroid

A single case of papillary adenocarcinoma of median ectopic thyroid is presented. There have been 96 other similar cases reported in the English literature. Since the tumor rarely involves the cervical lymphatics or thyroid gland in the absence of a palpable mass, local excision with the Sistrunk procedure is the recommended therapy. Suppression doses of thyroid hormone may be of benefit.

Tuberculosis of the larynx.

T UBERCULOSIS OF THE LARYNX is almost always associated with active pulmonary tuberculosis and has become a rare disease as a result of the effectiveness of antibiotic therapy. Until 1940 it occurred in 25%30% of patients having sputum positive for tubercle bacilli.3*5 Indeed, one of the authors, who was a radiologist in a hospital for tuberculosis, recalls that patients with tuberculous laryngitis were always at hand. By the late 1940s the incidence had diminished to 3%-6%. At present it is difficult to find an example. More importantly, it is now observed most frequently in elderly men, especially those with poor nutrition, many of whom are alcoholics with neglected cavitary pulmonary tuberculosis.’ In almost all instances, the disease results from tubercle bacilli carried to the larynx in the sputum from an active focus in the lungs.‘*2 The pulmonary lesion is usually exudative or caseating, and cavity formation is commonly observed. Occasionally, the bacilli may reach the larynx via the cervical lymphatics from an apparently benign tuberculous process in the pulmonary apex, producing scant sputum that is negative for acid-fast bacilli.3 Rarely, the larynx may be involved along with other organs in miliary tuberculosis.’ Primary tuberculous laryngitis is almost unknown6 The tubercle bacilli, carried in the sputum, tend to be deposited most often in areas of stratified squamous epithelium, ie, the posterior portions of the vocal cords and aryepiglotic folds, over the arytenoids, and on the epiglottis.‘,’ Columnar epithelium appears to be more resistant.4 Preexisting abrasions or inflammation are also favored sites.2 Once deposited, the bacilli burrow beneath the epithelium and initiate the formation of subepithelial microtubercles as well as a host reaction that is at first exudative with considerable edema. As the tubercles coalesce, there follows a proliferative and infiltrative process, the typical tuberculous granuloma, giving the mucosa a lumpy appearance. Further progression results in caseation, ulceration, and secondary infection.4 The infection may cause perichondritis and chondritis with additional swelling, especially of the arytenoids

Mangement of squamous cell carcinoma of the oral tongue and floor of mouth after excisional biopsy.

A review of the records of 23 patients with squamous cell carcinoma of the oral tongue and floor of mouth treated with irradiation after excisional biopsy has shown that: (a) Radiotherapy, primarily using interstitial radium implants, results in excellent local control of the primary area (100%) with preservation of function. (b) The frequency and severity of soft-tissue and bone necrosis may be reduced by not exceeding 5,500-6,000 rads from radium implants when only subclinical aggregates of cancer cells are probably present. (c) Theincidence of subsequent neck disease is low-8.7% (2 of 23 patients), and does not warrant routine elective irradiation of the cervical lymphatics.

Pulmonary lymphangiectasia demonstrated by lymphangiography in 2 patients with Noonan's syndrome.

Two cases of pulmonary lymphangiectasia associated with Noonan's syndrome are described. Chest films showed diffuse pulmonary intersitial infiltrates from infancy. Lymphangiograms demonstrated obstructive changes and collateral formation in the retroperitoneal, mediastinal, pulmonary, and cervical lymphatics and extensive opacification of the pulmonary and visceral pleural lymphatics. Possible mechanisms and causes of the lymphatic malformation are discussed.

Brugia pahangi Infections in Mongolian Jirds and Dogs Following the Ocular Inoculation of Infective Larvae

Infective larvae of Brugia pahangi collected from mosquitoes readily infected Mongolian jirds or dogs when placed on the intact eyeball. Histological studies in jirds showed that the larvae quickly penetrated into the orbital tissues. Further study in jirds showed that the larvae migrated rapidly via the veins or lymphatic vessels to the lungs, produced pulmonary ecchymotic hemorrhages within 5 min, and then accumulated in the pleural cavity where they induced a profuse pleural exudate. A considerable number of larvae persisted in the heart or pulmonary artery of jirds. Some of the larvae migrated to the cervical, iliolumbar, and renal lymphatics of jirds and a few larvae traveled to the peritoneal cavity. Thus, ocular inoculation of infective 3rd-stage larvae in jirds produced an infection predominantly of the heart, lungs, and pleural cavity. Third-stage larvae that had developed for 2 days in the peritoneal cavity of jirds were not infective for this host by ocular inoculation. Although inoculation of infective 3rd-stage larvae regularly induced patent infections in both jirds and dogs, the numbers of circulating microfilariae were low. Experimental infections of Brugia pahangi, a lymphatic-dwelling filaria, are usually achieved by the introduction of the infective thirdstage larvae by either the bite of infected mosquitoes or surgical methods such as syringe injection or inoculation onto artificial puncture wounds (Ewert and Singh, 1969). The subcutaneous route of larval inoculation by syringe is most commonly used for establishing infection. By this route, infections have been induced by injecting infective larvae in man (Buckley, 1958), lower primates, dogs, cats, and rodents (cf. reviews by Nelson, 1969; Ash and Riley, 1970). Successful infections were also produced in Mongolian jirds by intraperitoneal (McCall et al., 1973) and oral (Gwadz and Chernin, 1972) routes of infection. This paper presents evidence indicating that infective third-stage larvae of B. pahangi placed upon the corneal surface of the eye penetrate the conjunctival epithelium of jirds and dogs and subsequently produce patent infections Received for publication 29 May 1973. * Published as paper 1043, University of Georgia Institute of Comparative Medicine. This work was supported in part by the U. S.Japan Cooperative Medical Science Program, administered by the Geographic Medicine Branch, NIAID, Contract 69-92; Grant AI 09280 from NIAID, NIH; and in part by NIH-General Support Grant 3-R01-AM14901. t Department of Biology, Millersville State College, Millersville, Pa. $ Deceased. with microfilaremia. Observations on the migratory behavior and pathways of the early developing stages of the parasite are also presented. MATERIALS AND METHODS The animals used in this work were juvenile jirds (Meriones unguiculatus) procured from commercial sources and laboratory-reared mongrel dogs (Males, approximately 4 months old). Infective third-stage larvae of Brugia pahangi were obtained from Aedes aegypti (Liverpool strain) 10 days after the infective blood meals, by procedures previously described (Ah and Thompson, 1973). Inocula were prepared in Hanks' balanced salt solution (HBSS) by placing thoroughly washed infective larvae in 1-ml syringes. To permit prompt settling of larvae at the tip of the syringe barrel, the syringes containing the suspension were placed upright in the test tube rack. The larvae concentrated at the bottom of syringes were placed on the surface of the right eyeball of jirds by expelling a minute amount of HBSS. In dogs, drops of larval suspension were instilled onto the eyeball. Inoculations were done without anesthesia. Microfilarial counts were made by examining Giemsa-stained thick films of 20-mm3 samples of blood. At necropsy, all jirds were examined with the aid of a dissecting microscope. Generally, the protocol was as follows: (1) examination of all major lymphatic vessels and nodes, based upon prior studies of their location using Evans blue (Ah and Thompson, 1973); (2) examinations of heart blood, heart, lungs, and washings of pleural and peritoneal cavities; and (3) search of the subcutaneous tissues and removed skin, directly and by soaking. Recovery of the larvae from heart

Chylous Fistula: Complication of Neck Dissection

Chylous fistula, one case of which was associated with chylothorax, appeared in three patients. Attention is directed to the variations in the anatomical distribution of the cervical lymphatics. Evidence of chyle extravasation occurs within hours after neck dissection, and is not difficult to diagnose. Experience and surgical knowledge dictate that prompt exploration of the wound and control of the leaking areas by ligatures or pressure packing or both is indicated, although in certain less severe cases, external pressure and dietary control may be effective. In one case presented here, by the time reexploration was carried out, a chyloma had developed and it was impossible to identify the structures in the neck. An unusual treatment modality, surgical glue, was utilized to plug the fistula.

Lipid storage in cerebral pericytes in lymphogenic encephalopathy.

Intracellular membrane structures are subjected to a continuous renewal. Breakdown products are undoubtedly partly used for resynthesis locally, partly disposed of. The transport of lipoproteins is generally managed by the lymphatics [7]; in the brain, devoid of lymph vessels, prelymphatic pathways (substance of the basement membranes of the blood capillaries → Virchov-Robin’s intraadventitial spaces → intraadventitial spaces of cervical blood vessels → cervical lymphatics; 4) are fulfilling this task. Stasis of lymph-due lipoprotein molecules induces pericytes to incorporate them. In previous histochemical studies performed on the heart muscle, kidney, liver and intestine it has been shown that a regular consequence of lymphostasis is the appearance of ‘invisible’ lipids, derived from breakdown products of desintegrated cellular membrane structures (lipid phanerosis) [2]. The appearance of lipid droplets in pericytes can be regarded as a cerebral equivalent to this lipid phanerosis. In later stages of lymphogenic encephalopathy, collagenous and collagen-like fibers were seen in the substance of basement membranes [3]. Taking into account this fact and the marked alteration in lipid metabolism and the transport described above we feel justified in suspecting that lymphogenic encephalopathy may have some bearings on cerebral artherosclerosis.

Stage IA squamous cell carcinoma of the uterine cervix

The microscopic pathology and clinical courses of 44 patients treated with radical hysterectomy and pelvic lymphadenectomy for equivocal or early invasive squamous cell carcinoma of the cervix were reviewed according to the classification of Frick and his associates. The incidence of major therapy complications was 14 per cent and all patients survived 5 or more years after therapy. Review of the literature on Stage IA lesions showed a 1.9 per cent incidence of lymph node metastases (103 patients), a 0.4 per cent recurrence rate in 243 patients treated conservatively, and a 1.0 per cent incidence of recurrence or evidence of primary spread beyond the cervix in 621 patients receiving all forms of therapy. From reported results, it would appear that equivocally invasive lesions and those lesions invasive up to 3 mm. without involvement of cervical lymphatics can be managed safely with conservative therapy.

Lymphatics of the mouth and neck

Research evaluation in 125 dogs and twenty-five human subjects through visualization of lymphatics with sky blue dye has led to newer concepts in the lymph flow of the tongue, as well as the cervical lymphatics. Cannulation of the lymphatics of the tongue and injection with radiopaque material followed by cineradiography gives an insight into normal and abnormal flow patterns of the lymph drainage. The importance of the valves in the cervical lymphatics, cross over of lymphatics, and obstruction of the lymphatics has a definite bearing on the course of metastatic disease. The cervical lymphangiograms correspond well to the anatomy book descriptions except in two areas: first, the lymph drainage from the tip of the tongue did not go to the submental nodes; second, lymphatics originating near the midline of the tongue did not cross over to the opposite side except those near the tip of the tongue or if chronic obstruction was present. The application of lymphangiography to the study of the tongue, floor of the mouth, and neck lymphatics has brought us closer to specific anatomic and physiologic knowledge, which will give a better understanding of means to combat neoplasia in these areas.