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Minimal number of lymph nodes that need to be examined for adequate staging of colorectal cancer--factors influencing lymph node harvest.

BACKGROUND/AIMS: Accurate assessment of lymphatic node status is an essential component in staging of colorectal cancer and determining the need for adjuvant treatment. The risk of understaging nodal status decreases by increasing the number of examined lymph nodes. Several recommendations have been published for the minimum number of lymphatic nodes that need to be harvested for accurate nodal staging with minimal chance of error, ranging from 6 to 17 lymph nodes. However, the number of harvested lymph nodes is very variable, and this variability is poorly understood. The aim of this study was to determine factors associated with the number of retrieved lymph nodes in patients with colorectal cancer. METHODOLOGY: Clinical and histological characteristics of 177 patients operated for colorectal cancer were analyzed. RESULTS: In multiple regression analysis, male gender, better tumor differentiation and greater tumor size, as well as the presence of acute inflammation were determined as significant independent predictors of the increased number of resected and examined lymph nodes. CONCLUSIONS: The determination of the minimum number of lymph nodes required for accurate nodal staging of patients with colorectal cancer needs to be individualized.

Aged↗

Sites of lymph follicle formation in the draining popliteal lymph nodes of mice locally injected with antigenic and mitogenic substances.

Our previous studies showed that some antigenic and mitogenic substances, when locally injected into mice, efficiently produced new lymph follicles outside pre-existing follicles in draining lymph nodes, whereas others had virtually no effect. In the present experiments, young adult male mice were injected with several antigens and mitogens in the rear footpad, and the number and development sites of newly produced lymph follicles in the draining popliteal nodes were studied using serial sections of the nodes obtained between 5 and 21 days after injection. In the unstimulated state, each popliteal node contained a limited number of lymph follicles which mostly lay in a portion of the peripheral cortex overlaying the deep cortex (this portion is referred to as the PCOU), whereas a portion of the peripheral cortex extending beyond the deep cortex (referred to as the PCBU) was underdeveloped with only occasional follicles. Mice treated with soluble PHA or fluid tetanus toxoid developed germinal centers in association with existing follicles but failed to produce new follicles. The PCBU of the draining nodes remained underdeveloped, and the number and distribution pattern of lymph follicles within a draining node were comparable to those in the control node. Animals treated with LPS (50 micrograms), Con A, alum-precipitated PHA or alum-precipitated tetanus toxoid produced significantly large numbers of new follicles outside pre-existing follicles in the draining nodes, the new follicles produced in the PCBU being generally more numerous than those in the PCOU. In these draining nodes, the peripheral cortex, comprising a number of follicles, was found to overlie the deep cortex and extend beyond the deep cortex towards the hilar region. In animals given a less effective stimulant, such as ferritin or a smaller dose of LPS (10 micrograms), the draining nodes produced a relatively small number of new follicles, most of which were formed in the PCBU. The present results indicate that in the mouse popliteal node, the PCBU is morphologically underdeveloped under normal conditions, but develops lymph follicles in response to exogenous stimuli more readily than the PCOU, and that substances efficient in inducing follicle formation can be regarded as capable of stimulating the development of the peripheral cortex.

Animals↗

[Computed tomography of the soft tissues of the neck. Lymph node metastases and their differential diagnosis. I. Methods and the principal CT criteria for lymph node metastases].

Standardisation of the examination method is imperative to guarantee reproducible and valid assessability of the cervical lymph node status. To this end, update high-resolution CT equipment of the third generation will be suitable, provided it meets certain minimum requirements, such as: 120 kV, 280 mAs, 480 projections over 360 degrees, 4-5 mm slice thickness, continuous tomography. If a primary tumour is known to exist, no plain examination is needed. The decisive examination is effected after intravenous administration of contrast medium in a dosage of 2.0-2.5 ml contrast medium/kg body weight (assuming a body weight of 70 kg, this would amount to 150 ml = 45 g iodine), one-third of the total dosage to be given as bolus and two-thirds as a rapid infusion. This procedure ensures sharp definition of lymph nodes against vessels and musculature over the entire period of examination. If tumour anamnesis has been established the size of the lymph node is significant for assessing the lymph node status. Even lymph node metastases less than 15 mm can be properly identified if the structure of the lymph nodes is known and employed as a criterion (central hypodensity with rim enhancement, inhomogeneity).

Carcinoma, Squamous Cell↗

[advantages and disadvantages of three regional lymph node dissection of thoracic esophageal carcinoma and the lymph node dissection by thoraco-abdomino-midsternal approach].

The 117 cases of two regional (thoraco-abdominal) lymph node dissection were compared to the 56 cases of three regional (with neck area in addition) lymph node dissection for esophageal carcinoma. As for operative death and postoperative complications, there were no difference between these two groups. The prognosis of three regional dissecting group was better than that of two regional dissecting group concerning about the cases that lymph node metastases were less than 1 or 2, the depth of invasion was limited to just near adventitia (a1) and the locations were in upper or midthoracic esophagus. But also the rate of postoperative recurrence to the neck and uppermediastinal lymph nodes were high in spite of three regional dissection. Putting together with all cases, significant improvement of prognosis were not obtained in the three regional group compared to two regional group. So we thought the usual three regional lymph node dissection might not be sufficient. Recently we added midsternotomy and made the lymph node dissection in neck-thoracic junction more complete. This procedure did not make the operative death and postoperative complications increase and the improvement of prognosis was expected by it.

Abdomen↗

Studies on lymph humoral factor. Biological characteristics of a lymphocytopoietic factor in rat thoracic duct lymph.

The biological characteristics of a lymphocytopoietic factor obtained from rat thoracic duct lymph (Yamashita, Fukumoto & Miyamoto, 1976) were further investigated. The lymph extract from normal rats failed to stimulate both large pyroninophilic cell-proliferation and mitotic response in the spleen and lymph node of the thymectomized, irradiated and marrow reconstituted rat (B rat). This suggests that target or responsive cells for the factor are not marrow-derived (B) cells, but thymus-derived (T) cells. On the other hand, the lymph extract from the lymphopenic lymph-drained B rats showed similar high lymphopoietic activity to those of normal rats, indicating that the existence of a thymus is not essential for the production or secretion of the factor. The fact that lymphocytotic rats produced by syngeneic lymphocyte transfusion are most sensitive to the lymph extract suggests that liver endogenous level of this factor and the responsiveness of target cells are regulated by the number of circulating T lymphocytes.

Animals↗

[Effect of acid aspiration on right lymph duct lymph flow and prostaglandin metabolites in dogs].

Aspiration of acid gastric contents into the airways is a major cause of pulmonary injury. The author investigated the effects of intratracheal instillation of hydrochloric acid in the anesthetized dogs on pulmonary hemodynamics, pulmonary lymph flow and protein content, and stable metabolites of prostaglandin F2 alpha (PGF2 alpha), prostacyclin (PGI2) and thromboxane A2 (TXA2). The author measured the concentrations of 15-keto-13, 14-H2-PGF2 alpha, 6-keto-PGF1 alpha and TXB2 in blood and pulmonary (right duct) lymph by specific radioimmunoassay. After intratracheal instillation of 0.1 N HCL, 3 ml.kg-1, the right duct lymph flow increased significantly from 1.3 to 4.5 ml.h-1, and pulmonary lymph-to-plasma protein ratio increased significantly from 0.63 to 0.70. There was no significant change in hemodynamics after acid instillation. There was no significant change in arterial or mixed-venous blood levels of any of the three metabolites. After acid instillation, the right duct lymph concentrations increased 2-fold for PGI2 metabolite, 3-fold for TXB2, and 7-fold for PGF2 alpha metabolite. The flow of metabolites (concentration x flow) increased 13-fold for 6-keto-PGF1 alpha, 14-fold for TXB2, and 40-fold for PGF1 alpha metabolite. The author concludes that intratracheal instillation of hydrochloric acid in anesthetized dogs: 1) increases pulmonary microvascular permeability, and 2) stimulates the pulmonary generation of PGF2 alpha, prostacyclin and thromboxane, and that 3) the analysis of pulmonary lymph flow and its constituents is a useful means for the study of lung injuries.

Anesthesia, Intravenous↗

[Incidence of lymph node involvement in pN2 non-small cell lung carcinoma and reevaluation of the lymph node dissection method].

We reported post operative survival rate of 134 pN2 squamous cell carcinoma and adenocarcinoma patients in our institute, and analyzed the level of the mediastinal lymph node metastasis to evaluate the standard lymph node dissection method (R2b). Post operative survival rate showed no difference between the left and right lung carcinoma but it showed significant difference between the upper lobe and lower lobe of the both side. Compared with the upper lobe lung cancer, the lower lobe cancer showed higher incidence of metastasis to #7, #8 or #9 lymph node. It is suspected that lymph node dissection of ipsilateral #12 (U), contralateral hilar and #4 lymph node should be considered for the lower lobe cancer especially with #7 lymph node metastasis.

Adult↗

[Morphology of the lymph vessels and axillary and mediastinal lymph nodes of the white rat (Rattus norvegicus)].

In this work, the authors studied the morphology of the axillary and mediastinal lymph nodes and their efferent branches in the white rat (Rattus norvegicus). The main characteristics observed were: The presence of two groups of axillary lymph nodes, one in the lateral and the other in the medial portion, and the presence of two groups of mediastinal lymph nodes, one being ventrolateral and the other dorsoventral relating to cranial precava veins. Usually, in both sides, there is a lymphatic plexus dorsally to the jugulsubclavian angle, formed by reunion of internal jugular and subclavian trunks and the thoracic duct (to the left) or the right lymphatic trunk (to the right). From this plexus, one or two branches run off and flow into the venous jugulosubclavian angle. The subclavian trunk begins in the medial axillar lymph nodes and joins to the lymphatic plexus at the internal jugular trunk or at the thoracic duct or yet at the right lymphatic trunk according to the site, and finally it may link itself directly to the venous system. The mediastinal lymph nodes at the side send branches forming the right lymphatic trunk and branches adhering to the lymphatic plexus; the left lymph nodes join to the plexus or the thoracic duct.

Animals↗

Dynamic MR lymphangiography and carbon dye for sentinel lymph node detection: a solution for sentinel lymph node biopsy in mucosal head and neck cancer.

BACKGROUND: The practical application of sentinel lymph node biopsy in squamous cell carcinoma of the head and neck is restricted by the time sensitivity of blue dye and lack of spatial resolution and nonspecific node enhancement with radiocolloid. This study evaluates the use of magnetic resonance (MR) lymphangiography and carbon dye labeling to circumvent these limitations. METHODS: Gadomer/carbon dye mixture was injected into the tongue and stifle of adult swine (n = 4). MR lymphatic mapping was followed by intraoperative mapping with isosulfan blue dye. Sentinel lymph node biopsy and completion node dissection were performed 60 minutes after injection in four nodal basins and at 7 days after injection in eight. RESULTS: The technique was successful in all 12 nodal basins. The sentinel lymph nodes were stained black at the time of the immediate and delayed dissections. CONCLUSIONS: MR lymphangiography provides temporal and anatomic localization of the sentinel lymph node with a single investigation. Carbon dye is a sensitive and persistent visual marker of MRI-targeted sentinel lymph nodes.

Animals↗

Sentinel lymph node biopsy in melanoma patients with clinically negative regional lymph nodes--one institution's experience.

The purpose of this prospective study of sentinel lymph node (SLN) biopsy in a large series of melanoma patients with clinically negative regional lymph nodes from one cancer centre was to analyse the reliability of the procedure, the pattern of failures during follow-up and the factors affecting the clinical outcome of patients. Between April 1995 and November 2001, 726 consecutive patients with primary cutaneous malignant melanoma underwent SLN biopsy with preoperative lymphoscintigraphy. The vital blue dye technique was used in 170 patients, and the blue dye technique combined with intraoperative lymphoscintigraphy in 556 patients. The primary melanoma sites were head and neck in nine patients, the extremities in 419 patients, and the trunk in 298 patients. The median Breslow thickness was 3.0 mm. All patients were followed closely, the median follow-up time being 34 months. The sentinel node(s) were successfully identified in 96% of patients. Intraoperative lymphoscintigraphy combined with the blue dye technique improved the SLN identification rate (technical success in 97.3% of cases) compared with the blue dye technique alone (technical success in 91.6%). The rate of failed SLN procedures was significantly (P = 0.007) lower in inguinal basins (3.1%) compared with axillary basins (7.9%). SLN metastases were detected in 147 patients (20.2%). The presence of SLN metastases correlated significantly with primary tumour thickness and ulceration (P < 0.001). The false-negative SLN biopsy rate was 4.66% (27 out of 579 SLN-negative patients). All but two node-positive patients underwent complete lymphadenectomy. Lymph nodes other than SLNs were found to contain metastases in 26.9% of patients (39 out of 145). The 5 year overall survival (OS) rate was 84% for SLN-negative patients and 40% for SLN-positive patients. Five variables showed a strong, statistically significant negative independent prognostic association with OS: positive SLN status (P = 0.000001), primary melanoma thickness > 4 mm (P = 0.0009), male gender (P = 0.001), more than one lymph node involvement (P = 0.02) and lymph node extracapsular extension (P = 0.03). SLN biopsy is currently a valuable and effective diagnostic procedure for the precise staging of patients with clinically N0 cutaneous melanoma. So far SLN biopsy seems to be the only accessible method for consciously oriented detection of nodal micrometastases in melanoma that would otherwise go undetected. SLN status is the most important factor proven to distinguish high and low risk melanoma patients.

Adolescent↗

S-classification of sentinel lymph node biopsy predicts the results of complete regional lymph node dissection.

The purpose of this study was to identify melanoma patients with positive sentinel lymph nodes (SLNs) at increased risk for further metastases in this specific lymph node basin. A series of consecutive patients with primary malignant melanoma stage I and II were evaluated retrospectively. The results of SLN biopsy in 26 patients with positive SLNs were compared with those of complete regional lymph node dissection (RLND) using the recently published S-classification of SLNs. The results of S-classification of SLNs were correlated with the outcome of complete RLND. There was a significant correlation between the S stage of positive SLNs and the results of complete RLND (P=0.02). Only patients with SIII stage (n=4) SLNs were found to have further metastases in the residual lymph node basin. The present study indicates that patients with SI stage and SII stage SLNs rarely have further metastases in the specific lymph node basin.

Adult↗

Quality control of lymph node dissection in the Dutch randomized trial of D1 and D2 lymph node dissection for gastric cancer.

BACKGROUND: Variability among surgeons and reduced protocol adherence threaten the conduct and outcome of surgical multicenter trials. We introduced, in the Dutch Gastric Cancer Trial of D1 and D2 (extended) lymph node dissection for gastric cancer, a novel way of managing instruction, quality control, and evaluation of protocol adherence.METHODS: Of 1078 patients entered in the Dutch trial, 711 patients with potentially curative resections were evaluated. Numbers and locations of lymph nodes detected at pathological investigation were compared according to the guidelines of the Japanese Research Society for the Study of Gastric Carcer. Non-compliance indicated inadequate removal of lymph node stations, whereas contamination indicated that lymph nodes were detected outside the intended level of dissection. Protocol adherence during the course of the trial, and the impact on complications, hospital mortality, and survival were evaluated.RESULTS: Major non-compliance was noted in 15.3% of D1 and 25.9% of D2 patients. Contamination was present in 22.9% of D1 and 23.5% of D2 patients, and was limited to one or two lymph node stations only. Intensification of quality control resulted in only a marginal improvement in protocol adherence and in the number of lymph nodes detected. There was no association between protocol adherence and the occurrence of complications or long term survival.CONCLUSIONS: Contamination proved an important parameter to substantiate protocol adherence by the surgeon, whereas non-compliance had a multifactorial cause. Non-adherence to the protocol did not lead to increased hospital morbidity and mortality, but also had no impact on long term survival.

Journal Article↗

Histological differential diagnosis between lymph node toxoplasmosis and other benign lymph node hyperplasias.

The material from 667 lymph nodes, originally suspected of toxoplasmosis, was histologically re-examined, to evaluate criteria for diagnosis and differential diagnosis. The results showed that at least 80% of benign lymph node enlargements containing small groups of epithelioid cells were associated with high titres of Toxoplasma antibodies. Furthermore, 85--95% of the lymph nodes in association with high Toxoplasma antibodies showed the typical histological appearances of toxoplasmosis. The histological diagnosis of toxoplasmosis is thus both fairly specific and sensitive. Other lymph node lesions with small groups of epithelioid cells must be considered in the differential diagnosis. Sarcoidosis and tuberculosis usually have a predominance of distinct large epithelioid cell granulomata. Lymph nodes with sinus histiocytosis showing the formation of small groups of epithelioid cells, do not demonstrate prominent hyperplasia and include sparse germinal centres and were not associated with toxoplasmosis. Lymph nodes with disturbed general structure and small groups of epithelioid cells must be carefully assessed because of the significant possibility of malignancy.

Antibodies↗

High-frequency ventilation: lymph flow, lymph protein flux, and lung water.

The effects of high-frequency oscillatory (HFV) ventilation on lung fluid balance and microvascular permeability to macromolecules were measured in open-chest dog lungs. Prenodal lung lymph flow, concentration of total plasma proteins in lymph and plasma, pulmonary arterial and left atrial pressure, cardiac output, and blood-free lung wet-to-dry weight ratios were measured for conventional mechanical ventilation (CMV, 12/min, 200-300 ml tidal volume) and HFV of 15 Hz and a stroke volume of 40-50 ml for normal and elevated left atrial pressures. HFV increased both lymph flow and lung water (68 and 20%, respectively), and lymph-to-plasma ratios of total plasma proteins remained unchanged. When left atrial pressure was increased, an analysis of lymph protein flux indicates that the lung microvascular permeability was not altered by HFV. The increase in lymph flow and lung water associated with HFV may reflect an increased microvascular exchange surface area or a change in interstitial fluid pressure.

Animals↗

Comparison of accumulated allele loss between primary tumor and lymph node metastasis in stage II non-small cell lung carcinoma: implications for the timing of lymph node metastasis and prognostic value.

Although the Tumor-Node-Metastasis staging of non-small cell lung carcinoma (NSCLC) is the most effective predictor of survival, the clinical outcome of patients at each stage is variable on an individual case basis. We tested the value of incorporating information about the tumor heterogeneity of NSCLC into microsatellite allelotyping in a cohort of 48 node-positive stage II patients (T1N1M0 and T2N1M0). Microsatellite allelotyping involved microdissection of the invasive component of primary tumor and lymph node metastasis at multiple target sites followed by loss of heterozygosity (LOH) analysis at specific regions on chromosomes 1p, 3p, 5q, 7q, 8q, 9p, 10q, 17p, and 18q using 16 markers. All microsatellites manifested LOH ranging from 44 to 76% in primary tumor and showed various degree of heterogeneity between primary tumor and lymph node metastasis. LOH on 3p and 5q in the lymph node metastases was associated significantly with shortened survival of the patients (P = 0.033 and 0.004, respectively), whereas no single LOH in the primary tumors showed association with prognosis. For the analysis of the accumulated load of allele loss, fractional allele loss (FAL) was calculated for each sample. The maximal FAL of lymph node metastasis was significantly lower than that of primary tumor (P = 0.0015), possibly reflecting the early lymphatic spread. High maximal FAL of lymph node metastasis was significantly correlated with an adverse outcome (P = 0.012), whereas maximal FAL of primary tumor did not show any prognostic significance (P = 0.552). A composite mutational profile for each patient based on the allelotyping of the primary tumor and lymph node deposits may make a significant contribution to a more accurate prognosis of stage II NSCLC.

Aged↗

The resistance of a lymph node to lymph flow.

The relationship between lymph flow, lymph node arterial and venous perfusion pressure and lymph node resistance have been studied in an in vivo isolated canine iliac lymph node perfused through an afferent lymphatic with heparinized canine plasma. The relationship between the rate of perfusion and perfusion pressure across the node was linear but the calculated resistance of the node decreased as the rate of perfusion increased. In nine dogs the mean resistance to lymph flows less than 0.1 ml/min was 180 mmHg/ml min, but 68 mmHg/ml min to rates of perfusion above 1.0 ml/min. An increase of venous pressure in the veins draining the node increased the node's resistance by 8.6 mmHg/ml min for each 10 mmHg increase of venous pressure. The effect on node resistance of an increase of venous pressure was greater at low rates of perfusion. A decrease of arterial pressure in the arteries supplying the node reduced the node's resistance by 2 mmHg/ml min for each 10 mmHg decrease of arterial pressure. Increases of arterial pressure had an opposite effect of a similar magnitude. The effect on node resistance of a change of arterial pressure in either direction was greater at low rates of perfusion.

Animals↗

Sentinel lymph node versus axillary lymph node dissection for early-stage breast carcinoma: a comparison using a utility-adjusted number needed to treat analysis.

BACKGROUND: The current study was performed to compare the value of sentinel lymph node dissection (SND) and axillary lymph node dissection (AND) in improving the utility-adjusted survival for early-stage breast carcinoma patients. METHODS: A number needed to treat (NNT) analysis was used to compare SND with AND. In the NNT equation, 1/(S(SND) - S(AND)), S is the 5-year utility-adjusted survival. A literature review was performed to estimate 1) the prevalence of axillary lymph node disease for early-stage breast carcinoma, 2) the sensitivity and specificity of SND and AND, 3) the 5-year overall survival as a function of axillary lymph node involvement, 4) the risk of arm lymphedema as a function of the intervention performed, and 5) the utility correction (Uc; impairment of quality of life) for arm lymphedema. RESULTS: The NNT method of analysis favored SND over nearly the entire range of parameters with a sign change to a negative value occurring only as Uc becomes very close to unity. This suggests the superiority of the SND approach. Only when there is minimal loss of utility does AND become favored and then only minimally. CONCLUSIONS: Compared with AND, SND improves the utility-adjusted survival in patients with early-stage breast carcinoma. This finding is quite robust and was found to remain constant over a range of values for utility and lymph node prevalence.

Breast Neoplasms↗