Central Lymph Research Articles

A case with coincidental diagnosis of primary central nervous system lymphoma and lymph node sarcoidosis

Primary central nervous system lymphoma (PCNSL) is rare. Clinical and histological differential diagnosis of systemic lymphoma and sarcoidosis continues to be a challenge. The first case report in the German and English literature of PCNSL and synchronous sarcoidosis is presented. Synchronous mediastinal lymphadenopathy suggestive of non-Hodgkin's lymphoma (NHL) or sarcoidosis was noted. Both conditions require alternative therapeutic and prognostic considerations to PCNSL. A regime of intrathecal and adjuvant systemic chemotherapy led to transient clinical improvement prior to the patient's demise through overwhelming sepsis and multiorgan failure. Post mortem findings confirmed synchronous PCNSL with mediastinal lymph node sarcoidosis.

Is Prophylactic Central Compartment Lymph Node Dissection Necessary for Papillary Thyroid Carcinoma?

ABSTRACT The need for prophylactic central compartment lymph node dissection in patients with papillary thyroid carcinoma continues to be a subject of ongoing debate. Regional lymph node metastases are a common finding with papillary thyroid carcinoma, with an incidence as high as 50% or more. With the widespread use of high resolution ultrasound and sensitive thyroglobulin assays, lymph node metastases, not appreciated at the time of surgery, are showing up in the follow-up period, creating significant angst amongst patients, endocrinologists, and their surgeons. It was previously thought that lymph node metastases in papillary thyroid carcinoma had little bearing on survival, but this has more recently been challenged. Opponents of prophylactic central compartment node dissection cite high perioperative morbidity as a word of caution in performing prophylactic central neck dissections. The following review will look at the most up-to-date literature and best evidence for arriving at logical and sensible recommendations. This review will also look at specific definitions of what is a central compartment lymph node dissection. In the hands of experienced thyroid surgeons, prophylactic central compartment lymph node dissection, performed in a meticulous manner, can limit persistent or recurrent disease in the central compartment, and can diminish the need for routine administration of radioactive iodine, with acceptable perioperative morbidit

Antioxidant Protection and Lipid Peroxidation in the Lymph and Blood during Complete Freund’s Adjuvant-Induced Low-Grade Fever and Pyrogenal-Induced Fever

Experiments on rats showed that complete Freund's adjuvant-induced low-grade fever and pyrogenal-induced fever of different duration are accompanied by an increase in the content of lipid peroxidation products and components of the antioxidant system not only in blood plasma, but also in the central lymph. These changes reflect activation of drainage, evacuation, and transport function of the lymphatic system. We conclude that the lymphatic system plays an important role in the maintenance of the prooxidant-antioxidant balance under these pathological conditions.

Clinical factors related to central compartment lymph node metastasis in papillary thyroid microcarcinoma: clinical analysis of 117 cases

To analyze the correlation of central compartment lymph node metastasis (CCLNM) with different clinical factors of papillary thyroid microcarcinoma (PTMC). 117 patients of PTMC, 27 males and 90 females, aged 45 (16 - 68), underwent total thyroidectomy (or lobectomy) and central compartment lymph node dissection with or without lateral neck dissection. The correlation of CCLNM with age, sex, tumor size, tumor capsule, multifocality, and extrathyroid extension was analyzed. CCLNM was found in 42 of the 117 patients with the mean age of 40 +/- 9, significantly lower than that of the patients without CCLNM [(45 +/- 10), P < 0.05], and with the median tumor diameter of 0.75 cm, significantly longer than that of the patients without CCLNM (0.70 cm, P < 0.05). Both univariate and multivariate analyses showed that age and tumor size were significantly correlated with CCLNM (both P < 0.05). Classification tree analysis showed that the CCLNM rate of the patients younger than 43 was significantly higher than that of the patients older than 43. Sex, tumor capsule, multifocality, and extrathyroid extension were not associated with CCLNM. CCLNM occurs more frequently in the PTMC patients who are younger than 43 years and in those who have larger tumor.

Paravertebral extramedullary haemopoiesis associated with pyruvate kinase deficiency

A 62-year-old woman with known pyruvate kinase deficiency and previous splenectomy in early adulthood was investigated for breathlessness. A chest radiograph demonstrated a right retro-cardiac mass and computed tomography/magnetic resonance imaging scans confirmed a 56 · 37 · 60 mm heterogeneous soft tissue mass in the right paravertebral region at the T9/T10 level (top and bottom). The provisional diagnosis was of a neurogenic tumour and surgical excision was planned. Her full blood count at the time was as follows: haemoglobin concentration 101 g/l, white cell count 10AE76 · 10/l, platelet count 660 · 10/l and mean cell volume 105AE9 fl. Bilirubin was 28 lmol/l. She had been transfusion independent. At thoracotomy the mass appeared very vascular and adherent to the ribs and vertebra without bony erosion and with no involvement of nerve roots. The mass was completely excised at thoracotomy and microscopically was composed of varying proportions of mature adipocytes mixed with haemopoietic tissue with normal maturation. Extramedullary haemopoiesis is typically (>90% of cases) found in the liver and spleen in the context of myelofibrosis or thalassaemia but can occur rarely in the paravertebral area, central nervous system, eye, lymph nodes, myocardium, lung and pleura. There have been four previous reports of extramedullary haemopoiesis affecting the paravertebral area associated with pyruvate kinase deficiency with one case leading to spinal cord compression.

Clinically Related Factors and Features of Central Compartment Neck Lymph Nodes in Thyroid Micropapillary Carcinoma

Background and Objectives:Despite the overall excellent prognosis for patients with thyroid papillary microcarcinoma (PMC), PMC is associated with central compartment lymph node metastasis. The aim of this study is to evaluate the effect of clinical and pathological factors affecting the central compartment lymph node metastasis in thyroid PMC. Subjects and Method:We undertook a retrospective study of 161 patients treated between January, 2003 and June, 2007 for papillary thyroid microcarci- noma by total thyroidectomy and central compartment neck dissection (n=161) with or without comprehensive lateral neck dissection. Following factors were included to analyze the relationship of tumor size and central compartment lymph node meta- stasis;sex, age, extracapsular extension, lymphovascular tumor emboli, multifocality, bilaterality, AMES risk group, lateral cervical lymph node involvement. Results:In 109 of 161 patients (67.7%), tumor size between 5-10 mm was significantly related with extracapsular extension (p=0.027) and also with the AMES high risk group (p=0.007). In 75 of 161 patients (46.6%), central compartment lymph node metastasis were found. By univariate analysis, tumor multifocality, bilaterality, and lateral lymph node involvement were related with central compartment lymph node metastasis. But on multivariate analysis, tumor bilaterality (p=0.008) and lateral lymph node involvement (p=0.018) were significantly related with central compart- ment lymph node metastasis. Conclusion:Prophylactic neck dissection of central compartment lymph nodes in PMC should be recommended as a routine procedure particularly for patients with tumor bilaterality and metastatic lymph nodes in the lateral neck. (Korean J Otorhinolaryngol-Head Neck Surg 2009;52:232-6)

Clinical Characteristics of Multifocal Papillary Thyroid Carcinoma

Background and Objectives:Papillary thyroid cancers (PTCs) often present as multifocal tumors. Whether multifocal tumors are associated with increased risk of recurrence and mortality is still the subject of controversy. The aim of current study was to indi- vidualize factors associated with multifocality of papillary thyroid cancer and determine the clinical significance of multifocal thy- roid cancer. Subjects and Method:We undertook a retrospective study of 403 patients treated between January, 2003 and June, 2007 for papillary thyroid carcinoma by total thyroidectomy and central compartment neck dissection (n=403) with or without comprehensive lateral neck dissection. There were 342 women and 61 men whose mean age was 47.3 years old. Following criteria were used to study the pattern of and factors related with multifocality:sex, age, extracapsular extension, central compartment lymph node metastasis, the involvement of lateral neck lymph node, AMES risk group, distant metastasis. Results:Of those fac- tors, sex (p=0.0481), central compartment lymph node metastasis (p=0.0007), the involvement of lateral neck lymph node (p=0.0001) were significantly related factors for multifocality of papillary thyroid cancer. Age, primary tumor size, AMES risk group were not significantly related with multifocality. Bilateral or contralateral central compartment lymph node metastasis oc- curred more frequently in multifocal PTCs (64.0%) than solitary PTCs (46.9)(p=0.012). Conclusion:Our data suggest that the multifocal tumors in patients with papillary thyroid carcinoma are associated with increased risk of bilateral central compartment and lateral cervical lymph node metastasis. Therefore, total thyroidectomy and bilateral central compartment lymph node dissection should be recommended as a routine procedure in multifocal papillary carcinoma. (Korean J Otorhinolaryngol-Head Neck Surg 2009;52:512-5)

Clinical Characteristics of Thyroid Micropapillary Carcinoma

Background and Objectives Thyroid micropapillary carcinoma (equal or less than 10 mm at great dimension) is now reported with increasing incidence due to fine needle aspiration under high-resolution ultrasonography. The extent of thyroidectomy and lymph node dissection has been an issue of controversy. The purpose of this study was to analyze clinical characteristics of thyroid micropapillary carcinoma with total thyroidectomy and preventive central neck dissection. Subjects and Method For suspicious thyroid micropapillary carcinoma, total thyroidectomy and preventive central neck dissection was performed in 63 patients (18 male, 45 female, mean ages of 59 years) between November 2004 and September 2008. They were suspected to have micropapillary carcinoma by fine needle aspiration and diagnosed with micropapillary carcinoma postoperatively. Results The mean tumor size was 6 mm. Twenty-one patients (33.3%) had multifocal diseases and 19 patients (30.2%) had extrathyroid extension. Lymph node metastases were found in 20 patients (31.7%) on central neck and 7 patients (11.1%) on lateral neck. There were no relations between multifocal disease or extrathyroid lesion and lymph node metastases (p>0.05). There was no significance of variables according to tumor size of 5 mm (p>0.05). There was a significant relation between central and lateral lymph node metastasis (p

Pro- and Antioxidants in the Central Lymph in Experimental Chronic Toxic Hepatitis

Using rat model of chronic toxic hepatitis we showed the involvement of the lymph system in the formation of the response to toxic liver damage consisting in deposition of LPO products in the central lymph and active involvement of antioxidants in their neutralization with redistribution of ceruloplasmin into lymph vessels against the background of reduced a-tocopherol content in the central lymph.

Minimally invasive video-assisted central compartment lymph node dissection

Central compartment lymph node dissection is mandatory in several thyroid tumors together with total thyroidectomy: medullary thyroid carcinoma and high-risk papillary carcinomas are the most common indications. Minimally invasive video assisted thyroidectomy is not indicated for high risk carcinomas; only low-risk papillary carcinomas and prophylactic thyroidectomy in RET gene mutation carriers, among malignancies, should be approached endoscopically. For this reason it was presumed that, if surgeons also are prone to perform minimally invasive video assisted thyroidectomy in these cases, it was necessary to remove the lymph nodes of level VI via the same access, at least in selected cases where this was possible. Here we describe and discuss the minimally invasive video assisted technique for central compartment lymph node dissection.

Papillary Thyroid Microcarcinoma - Own Experience

Papillary thyroid microcarcinoma is a particular form of cancer of the thyroid gland. This term, according to the WHO classification, is applied to papillary tumors no larger than 1.0 cm in diameter, which are incidentally detected during the postoperative histopathological examination. In clinical practice, the term pertains to all papillary tumors of the size smaller than or equal to 1 cm. The aim of the study was to determine the prevalence of papillary thyroid microcarcinoma and its selected histopathological characteristics among patients with malignant cancer of the thyroid gland identified in our own material in the years 2000-2007. Material and methods. The study included 523 patients treated for thyroid carcinoma: 401 (76.7%) women and 122 (23.3%) men aged 12-83 years (mean 49.8 years). Surgeries were carried out according to the Polish Group for Endocrine Carcinomas recommendations, in compliance with the European consensus. Results. Papillary thyroid carcinoma was identified in the postoperative histopathological examination in 391 (74.8%) patients; 285 (72.9%) women and 106 (27.1%) men. Their age ranged from 14 to 75 years (mean 49.3 years). Among 391 cases, tumor progression classified according to the WHO criteria (3) was as follows: T1 in 260 (66.5%), T2 in 59 (15.1%), T3 in 53 (13.5%) and T4 in 19 (4.8%) patients. In 150 cases (38.4% of papillary tumors), the tumor fulfilled the morphological criteria for microcarcinoma (4) and was detected in 118 (78.7%) women and 32 (21.3%) men. Carcinoma was identified in the neutral goiter in 138 cases, and in 12 patients in hyperactive, including 9 in nodular and 3 in Graves’ goiters. The disease was suspected or diagnosed preoperatively or at surgery in 112 patients. Postoperative diagnosis was performed in 38 (25.3%) individuals with micrcarcinoma. Twenty-four (38%) of 63 patients with multifocal tumors were subjected to adjunctive surgery as their cancer diagnosis was made only postoperatively in the histopathological examination. The subcapsular location of microcarcinoma was found in 78 (49.4%) cases including capsular infiltration and extracapsular invasion in 14 patients. The exact histopathological examination showed multifocality in 63 (42%) cases and involvement of the local lymph nodes in 29 (19.3%) patients. In 21 cases, the central compartment lymph nodes were involved. The presence of metastases in the central and lateral lymph node compartment was observed in 5 cases; in 3 patients skip metastases were detected in the lateral compartment on the tumor side omitting the central compartment. No patient with microcarcinoma diagnosed between the years 2000 and 2007 revealed distant metastases. Conclusions. Due to contemporary diagnostics, papillary thyroid microcarcinomas – tumors up to 1 cm – are most commonly identified cancers of the thyroid gland. High accuracy of US-guided fineneedle aspiration biopsy of high resolution permits to diagnose the majority of these tumors prior to surgery.

Outcome of reoperation for thyroid cancer: clinical analysis of 72 cases

To analyze the indication of reoperation of thyroid cancer and to explore the timing, surgical pattern of reoperation. Protocols of 72 patients underwent reoperation of thyroid cancer from June 2003 to August 2006 were reviewed retrospectively. Causes for reoperation were as follows: residue of the tumor locally as the inappropriate initial operation; local recurrence and cervical lymph node metastasis; before (131)I ablation which differentiated thyroid cancer with distant place metastasis. The reoperation style included residual lobectomy plus isthmus with single tumor below 2 cm, total thyroidectomy in most the other conditions and selective lymph node dissection in finding or suspected cervical lymph node metastasis. The rate of residual in thyroid confirmed by postoperative pathology was 47.1% (32/68). The rate of residual in cervical lymph node was 81.4% (35/43). The rates of temporary and permanent laryngeal recurrent nerve injury were 5.6% (4/72) and 1.4% (1/72) respectively. The rates of temporary and permanent hypocalcemia were 26.4% (19/72) and 1.4% (1/72) respectively. Inadequate operation, local recurrence and cervical lymph node metastasis of thyroid cancer need revision surgery undoubtedly. The optimal treatment was total thyroidectomy and level VI, VII central compartment lymph node dissection plus intraoperative frozen-section evaluation.

The Importance of Central Compartment Elective Lymph Node Excision in the Staging and Treatment of Papillary Thyroid Cancer

The Importance of Central Compartment Elective Lymph Node Excision in the Staging and Treatment of Papillary Thyroid Cancer

Pretargeted Anti–Carcinoembryonic-Antigen Radioimmunotherapy for Medullary Thyroid Carcinoma

significant survival advantage of patients with progressive medullary thyroid carcinoma treated with pretargeted anti–carcinoembryonic-antigen radioimmunotherapy over an untreated control group matched on calcitonin doubling time (median, 110 months v 61 months; P .030). This survival advantage doubled for biologic responders relative to these controls (median, 159 months v 61 months; P .010), and was still evident when biologic responders were compared with biologic nonresponders (median, 159 months v 109 months; P .035). In delineating clinical risk, Chatal et al relied on calcitonin doubling times, with cut-offs set at 2 years and 5 years. In clinical practice, however, a risk classification based on calcitonin doubling times may not really be helpful because of the need for protracted expectant observation. Anti–carcinoembryonic-antigen radioimmunotherapy is targeted on membrane-bound carcinoembryonic antigen. There is some evidence to suggest that serum levels of carcinoembryonic antigen from patients with medullary thyroid carcinoma may correspond to the expression of carcinoembryonic antigen in the cancer cells. 2,3 In addition, the duration of response to pretargeted anti–carcinoembryonic-antigen radioimmunotherapy was previously shown to correlate with the duration of the blood carcinoembryonic antigen response. 4 The suitability of serum levels of carcinoembryonic antigen for risk stratification of patients with medullary thyroid carcinoma before initial operation has emerged only recently. 5 Preoperative serum levels of carcinoembryonic antigens greater than 30 ng/mL almost always conflicted with surgical curability and were associated with an approximately 70% rate of involvement of the central and lateral lymph node compartment on the side of the primary tumor. This rate of involvement increased to approximately 90% when the preoperative serum level of carcinoembryonic antigen exceeded 100 ng/mL. In this setting, involvement of the lateral lymph node compartment on the side opposite to the primary tumor, and distant metastases were seen in three quarters of the patients at the time of operation. 5 These data suggest that pretherapeutic serum levels of carcinoembryonic antigen, which are available within a few days, may predict the chance of patients with medullary thyroid carcinoma to benefit from anti– carcinoembryonic-antigen radioimmunotherapy. We wonder if Chatal et al have the data to break down their patients with medullary thyroid carcinoma by pretherapeutic serum level of carcinoembryonic antigen and response to pretargeted anti– carcinoembryonic-antigen radioimmunotherapy. This piece of information would further elucidate the effectiveness of this novel therapeutic modality in select subgroups of patients with medullary thyroid carcinoma.

The effect of experimental haemorrhagic shock on the bacterial content of thoracic duct lymph.

The effect of haemorrhagic shock on the simultaneous appearance of enteric micro-organisms in the central lymph and the portal blood was studied in 30 dogs. Irreversible haemorrhagic shock results in portal bacteraemia but the lymph remains sterile. Thoracic duct drainage is harmful and hastens the onset of irreversibility.

The role of nuclear factor-kappa B in bacterial translocation in cholestatic rats

Xanthinoxidase (XO) derived radical species are involved in bacterial translocation (BT) in cholestatic rats. The mechanism by which XO influences remains unclear. It has been shown recently that nuclear factor-kappa B (NF-kappaB), a ubiquitous transcription factor, can be activated by oxidative stress and thereby promote the process of BT. We investigated the effects of NF-kappaB inactivation on the incidence of BT in cholestatic rats. Sprague-Dawley rats were randomly assigned to one of eight groups: groups 1-4 were sham laparotomized rats either untreated (S1) or treated for 5 days with thalidomide (S2), curcumin (S3), or Inchin-ko (ICK; S4); groups 5-8 underwent common bile duct ligation (CBDL) for 5 days and were either untreated (C1) or treated with thalidomide (C2), curcumin (C3), or ICK (C4). After 5 days bacteriological cultures were performed from portal blood and V. cava, from the central mesenteric lymph node complex (MLN), spleen, and liver. The intensity of the activated NF-kappaB-subunit p65/p50 in the ileum mucosa was estimated by light microscopy and a scoring system from 1 to 20. Malondialdehyde (MDA) and myeloperoxidase activity (MPO) in the ileum were evaluated and expressed as U/g dry weight. Thalidomide and ICK reduced in CBDL-rats significantly the BT rate (63% vs. 18%, 63% vs. 30%, P<0.01). Enzyme estimations (MDA, MPO, and GSH) in sham operated animals showed no significant changes in the untreated groups compared with the treated groups. CBDL-rats pre-treatment with all three compounds caused a significant increase of MDA levels if groups were compared with the untreated C1-group (C1 31.6+/-7.7, C2 54.5+/-12.2, C3 53.3+/-11.2, and C4 47.2+/-9.4). GSH was reduced after the pre-treatment by all compounds but only significantly after curcumin pre-treatment (C1 vs. C3: 13.9+/-1.8 vs. 7.1+/-1.8; P<0.05). MPO estimations were significantly higher in the untreated C1-group if compared with groups C2, C3, and C4 (C1 1036.4+/-340.9, C2 709.9+/-125.9, C3 545.2+/-136.6, and C4 556.7+/-247.4; P<0.05). Thalidomide inhibited significantly the activation of NF-kappaB (C2 vs. C1: 6.0+/-4.5 vs. 12.7+/-5.3; P<0.01). Likewise, Curcumin and ICK suppressed NF-kappaB activation, but this did not reach significance in this experiment. NF-kappaB is involved in the process of BT in cholestatic rats and may be activated by XO derived ROS. We assume that the activated NF-kappaB initiates transcription of target genes inducing cytokine production, which in turn disrupts the tight junctions leading to BT from the intestinal lumen to the MLNs and circulation.

A less invasive, selective, functional neck dissection for papillary thyroid carcinoma

To describe an alternative lateral neck access in order to perform neck dissection in papillary thyroid carcinoma (PTC) with lymph node involvement. Prospective (January 2000 to December 2003), 36-month study. Catholic University of Rome and University of "Tor Vergata", Rome, Italy. Twenty-four consecutive patients with PTC and cervical lymph node metastases were included. Functional neck dissection (FND), unilateral or bilateral, was performed acceding via a lateral dissection through a traditional Kocher incision, running along the superficial fascia of the neck and posteriorly to the sternocleidomastoideus muscle. Mean age was 39.04+/-13.69 years. Twenty patients were women and four were men. Mean tumour size was 2.5+/-1 cm, while the greatest metastatic lymph node size was 4.5 cm. Minimally invasive, selective FND was performed in all patients associated to total thyroidectomy and central compartment lymph node clearance. Metastatic lymph nodes were found in 142 out of 340 of the lymph nodes dissected. Minimally invasive neck dissection seems to carry a lower risk in terms of specific morbidity and allows a quicker recovery and a better aesthetic result. This access has to be considered as a less invasive procedure compared to the other surgical accesses for the radical or modified lateral neck dissection.

Lymphatic Absorption Is the Primary Contributor to the Systemic Availability of Epoetin Alfa following Subcutaneous Administration to Sheep

The contribution of the lymphatics to the absorption and systemic availability of recombinant human epoetin alfa (rHuEPO) following s.c. injection was examined using a cannulated sheep model. Parallel studies were conducted in sheep where a single bolus dose was administered either by i.v. (10, 100, or 1000 IU/kg) or s.c. (400 IU/kg) injection. The first s.c. group served as a control for the calculation of absolute bioavailability. In the second group, the efferent popliteal lymphatic duct was cannulated and peripheral lymph draining the injection site was continuously collected. In the third group, the thoracic duct was cannulated to allow collection of central lymph just prior to entry into the systemic circulation. Blood was periodically sampled from all animals, and concentrations in serum and lymph were determined by enzyme-linked immunosorbent assay. The cumulative amount of rHuEPO recovered in peripheral and central lymph was 83.9 +/- 6.6% and 75.3 +/- 3.9% of the administered dose, respectively, indicating almost complete absorption from the s.c. injection site and minimal clearance during transit through the lymphatic system. After i.v. administration, the systemic clearance of rHuEPO decreased with increasing dose, reflecting capacity-limited elimination kinetics. A pharmacokinetic model was developed to simultaneously fit experimental data for all treatment groups and estimate bioavailability. The direct measurement of >75% of the dose in peripheral and central lymph independently verifies the calculated bioavailability of 87% and demonstrates the major role of the lymphatic route in the overall s.c. bioavailability of rHuEPO after s.c. administration with this animal model.

Sentinel lymph nodes study in 30 cases of melanoma.

In 30 cases of melanoma, we attempted to detect sentinel lymph nodes using 1-2% patent blue dye and were able to detect them in 27 cases (90%): 19 cases out of 21 cases in the groin area (90%), 5 out of 5 cases in the axilla area (100%), and 3 out of 4 cases in the neck area (75%). The numbers of sentinel lymph nodes were one in 16 cases, two in 7 cases, three in 2 cases, and four in 2 cases. The cases with three and four nodes were all in the groin area. In 22 cases, tumor metastasis was negative in sentinel lymph nodes. Sentinel lymph nodes were detected in 36 out of 174 samples, and tumor metastasis was negative except in these sentinel lymph nodes (false negative 0%). In the groin area, sentinel lymph nodes were located around the femoral and great saphenous vein junction. In the axilla area, sentinel lymph nodes were located in the central, lateral and subscapular lymph nodes. In the head and neck area, sentinel lymph nodes were found in the submandibular and occipital lymph nodes. The positions of sentinel lymph nodes differed a little with tumor location. By accumulating cases, it should become possible to predict the positions of sentinel lymph nodes before operations. Sentinel lymph node biopsy is easy and requires only a small incision.

Systemic Availability and Lymphatic Transport of Human Growth Hormone Administered by Subcutaneous Injection

Degradation of human growth hormone (hGH) at the injection site has previously been implicated as the basis for its reduced systemic availability following subcutaneous (SC) administration. The goal of these studies was to develop an animal model which would allow mass balance calculations to (i) quantify the loss at the injection site and (ii) determine the role of the lymphatics in the transport of subcutaneously‐administered hGH. The animal model utilized a sheep and enabled simultaneous sampling of blood and collection of either peripheral lymph (via the efferent duct of the popliteal lymph node draining the injection site) or central lymph (via the thoracic lymph duct). In non‐lymph cannulated sheep, the systemic availability of hGH following SC dosing was 58.4 ± 9.1% (mean ± SEM) relative to an intravenous (IV) control. The availability of hGH decreased to approximately 30–40% when either peripheral or central lymph was collected indicating that a proportion of the dose was transported via the lymph. The fraction of the administered dose collected in peripheral lymph was 61.7 ± 8.5% (mean ± SEM), whereas only 8.6 ± 1.3% was collected in central lymph. These results suggested that loss of hGH within the lymphatics contributed significantly to its reduced systemic availability following SC administration. The total recovery (sum of the systemic availability and the cumulative amount recovered in lymph) of hGH was approximately 93% of the dose in the peripherally‐cannulated group indicating that loss at the injection site was minimal. © 2000 Wiley‐Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 89: 168–177, 2000