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[Analysis of lymph node status and lymph node morphology in cervix cancer operated by the Wertheim-Meigs-Okabayashi method].

We evaluated in the histologic labor, of the Department of Obstetrics and Gynaecology of the Tübingen University 133 specimens of cervical carcinomas stages I and II operated on according to Wertheim-Meigs-Okabayashi. Topic of this analysis is lymph node status, concomitant alterations and lymphangiosis carcinomatosa. On the average 22.1 lymph nodes (1-58) have been removed. 12.8 per cent of cervical carcinomas had metastases, on the average 3 ones. 78.6 per cent of the metastases were localized in nondilymphatici interiliaci, 14.3 per cent in nodi iliaci communes. 5-year survival with metastases was 70.6 per cent, without 90.5 per cent. Over all a lymphangiosis carcinomatosa in 20.3 per cent was detectable. In 59.9 per cent of the lymph node metastases additionally a lymphangiosis carcinomatosa was present, on the contrary only 9.9 per cent of tumour-free ones. 5-year survival with lymphangiosis carcinomatosa was 70.4 per cent and 92.4 per cent without. Regressive changes, mostly as vacat fat, were observed in like the same percentage both in tumour positive and tumourfree lymph nodes.

Adenocarcinoma↗

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↗

[Reactive enlargement of cervical lymph nodes and cervical lymph node metastases: sonography (M/Q quotient) and computed tomography].

Ranking of sonographic maximum/transverse diameter quotients was compared with the ranking of CT in respect of identification and exclusion of cervical lymph node metastases. Both sonography and CT are distinguished by a high degree of sensitivity in the imaging of cervical lymph node metastases. Sonography, with the assistance of the maximum/transverse diameter quotient, can differentiate between benign enlarged and non-enlarged lymph nodes on the one hand and cervical lymph node metastases on the other, with a safety of 95 per cent. CT can yield definite information regarding the tumour status only after contrast medium administration under the criteria of central hypodensity and peripheral marginal enhancement. CT is much less specific than the sonographic M/T quotient (66% vs 95%). Accuracy of sonography (94%) is clearly superior to that of CT (79%).

Adult↗

Role of T and NK cells and IL7/IL7r interactions during neonatal maturation of lymph nodes.

Lymph node (LN) development depends on prenatal interactions occurring between LN inducer and LN organizer cells. We have distinguished defects in LN formation due to failure in embryonic development (aly/aly) from defects in postnatal maturation (Il2rgamma(-/-)Rag2(-/-)). Both mutant strains form normal primordial LNs with differing fate. In aly/aly mice, the LN primordium dissipates irreversibly late in gestation; in contrast, Il2rgamma(-/-)Rag2(-/-) LN anlage persists for a week after birth but disperses subsequently, a process reversible by neonatal transfer of WT IL7r(+) TCR(+) T or natural killer (NK) cells, suggesting a role for IL7/IL7r interactions. Thus, we reveal a unique stage of postnatal LN development during which mature lymphocytes and IL7/IL7r interactions may play an important role.

Adoptive Transfer↗

Immunohistochemical and immunoelectron microscopic localization of S-100 protein in the interdigitating reticulum cells of the human lymph node.

Lymph nodes of 5 cases with non-specific lymphadenitis and of 4 cases with dermatopathic lymphadenitis were examined by the peroxidase anti-peroxidase (PAP) method and by immunoelectron microscopy using monospecific antibody against nervous system specific S-100 protein. S-100 protein was detected in dendritic shaped cells of the thymus-dependent area of non-specific lymphadenitis. The paracortical area of dermatopathic lymphadenitis showed a marked accumulation of S-100 protein-containing dendritic shaped cells. Immunoelectron micrographs revealed that S-100 protein-containing dendritic shaped cells of both non-specific and dermatopathic lymphadenitis corresponded to interdigitating reticulum cells (IRC). The detection of S-100 protein in the nucleus and on the cytoplasmic and nuclear membrane suggested that IRCs themselves synthesized S-100 protein. S-100 protein is a very useful cell marker for the identification of IRC in the lymphoid tissue.

Cell Nucleus↗

The microanatomic location of metastatic melanoma in sentinel lymph nodes predicts nonsentinel lymph node involvement.

PURPOSE: Sentinel node biopsy is now widely accepted as the most accurate prognostic indicator in melanoma, and is important in guiding management of patients with clinical stage I or II disease. Patients with a positive sentinel node have conventionally undergone completion lymphadenectomy (CLND) of the involved basin, but only 20% have involvement beyond the sentinel node, suggesting that CLND may be unnecessary for the other 80% of patients. This study seeks to identify criteria that might be used to be more restrictive in selecting those who should undergo CLND. METHODS: A total of 146 patients were identified who had had a positive sentinel node biopsy for malignant melanoma. Their sentinel nodes and lymphadenectomy specimens were re-evaluated pathologically. The metastatic melanoma in each sentinel node was assessed according to its microanatomic location within the node (subcapsular, combined subcapsular and parenchymal, parenchymal, multifocal, or extensive), and this was correlated with the presence of involved nonsentinel nodes in the CLND. The depth of the metastases from the sentinel node capsule was also recorded. RESULTS: The metastatic deposits in the sentinel node were subcapsular in 26.0% of patients. None of these patients had any nonsentinel nodes involved on CLND. In the patients whose sentinel node metastases had a different microanatomic location, the rate of nonsentinel node involvement was 22.2% overall. CONCLUSION: The microanatomic location of metastases within sentinel nodes predicts nonsentinel lymph node involvement. In patients with only subcapsular deposits in the sentinel node, it is possible that CLND could safely be avoided.

Female↗

Predictors of positive axillary lymph nodes after sentinel lymph node biopsy in breast cancer.

OBJECTIVE: The purpose of this study was to determine the factors that predict the presence of metastasis in nonsentinel lymph nodes (SLN) when the SLN is positive. METHODS: A prospective database was analyzed and included patients who underwent SLN biopsy for invasive breast cancer from July 1997 to August 2000 (n = 442). One hundred (22.6%) patients had one or more positive SLNs, and were analyzed to determine factors that predicted additional positive axillary nodes. RESULTS: Of the 100 patients with a positive SLN, 40 patients (40%) had additional metastasis in non-SLNs. The only significant variables that predicted non-SLN metastasis were tumor lymphovascular invasion (P = 0.004), extranodal extension (P < 0.001), and increasing size of the metastasis within the SLN (P = 0.011). In analyzing just those patients who had lymphovascular invasion, extranodal extension, and a SLN metastasis > 2mm, 92% were found to have additional positive nodes. CONCLUSIONS: In patients with invasive breast cancer and a positive sentinel lymph node, lymphovascular invasion, extranodal extension, and increasing size of the metastasis all significantly increase the frequency of additional positive nodes.

Adult↗

Sentinel lymph node biopsy alone without axillary lymph node dissection--follow up of sentinel lymph node negative breast cancer patients.

AIMS: To evaluate the rate of axillary recurrences in sentinel lymph node (SLN) negative breast cancer patients after sentinel lymph node biopsy (SLNB) alone without further axillary lymph node dissection (ALND). METHODS: Between May 1999 and February 2001 all patients who had primary invasive breast cancer and were SLN negative were eligible for this prospective study. SLNB was performed by using the combined method with radioactive tracer and blue dye. SLNs were examined by frozen section, standard H/E staining and immunohistochemistry staining. SLN negative patients did not receive further ALND. Follow-up was done three-monthly with clinical controls, blood samples and ultrasound of the breast and axilla. An annual mammogram was performed. RESULTS: 116 patients with T1 or T2 invasive breast cancer were included in this trial. All 116 patients had negative SLNs in frozen sections, in H/E staining and in immunohistochemistry staining. The mean number of removed SLNs was 2.03+/-1.22. Mean tumor size was 17.15+/-7.62 mm. Postmenopausal patients totalled 79.3 and 20.7% of patients were premenopausal. No local or axillary recurrences occurred at a mean duration of follow-up of 22.12+/-6.38 months. CONCLUSION: The absence of axillary recurrences after SLNB without ALND in SLN negative breast cancer patients supports the hypothesis that SLNB is accurate and safe while providing less surgical morbidity. Short term results are very promising. SLNB without ALND in SLN negative patients is an excellent procedure for axillary staging in a cohort of breast cancer patients with small tumors.

Adult↗

A high number of tumor free axillary lymph nodes from patients with lymph node negative breast carcinoma is associated with poor outcome.

BACKGROUND: Lymph node metastasis is the oldest and most reliable prognostic indicator in breast carcinoma. In the absence of tumor metastasis, draining lymph nodes can undergo hyperplasia, resulting in increases in the number and size of detectable lymph nodes. The prognostic value of this process has never been established. Lymph node negative breast carcinoma provides a unique opportunity to study the downstream effects of increased lymphatic drainage and lymph node hyperplasia. METHODS: The authors studied 290 cases of lymph node negative breast carcinoma and provided patients with a median of 103 months of follow-up. The number of tumor free lymph nodes in ipsilateral axillary resections, as well as 10 traditional histopathologic markers, were analyzed for their prognostic value. RESULTS: The cohort was divided into quartiles according to the number of tumor negative lymph nodes. The 5-year survival for patients with 20 or more tumor free lymph nodes (top quartile) was 84.7%, compared with 96.3% for patients with fewer than 20 tumor free lymph nodes. The 5-year relative risk of dying of metastatic disease in the top quartile was 3.61 (95% confidence interval, 1.37-9.52, P = 0.01), independent of necrosis, tumor size, patient age, nuclear and histologic grade, lymphocytic infiltrate, and lymphovascular invasion. The absolute lymph node number was highly associated with the presence of necrosis in invasive tumor. CONCLUSIONS: The number of tumor free lymph nodes is a novel, independent predictor of aggressive disease in cases of lymph node negative breast carcinoma. This finding may be a biologic function of host-derived, and possibly tumor-derived, lymphangiogenic cytokines.

Adult↗

Identification of cell types present in bovine haemolymph nodes and lymph nodes by immunostaining.

Mediastinal haemolymph nodes (HN) and lymph nodes (LN) of 15 healthy calves and ten healthy steers and 53 steers with respiratory diseases (pneumonias) were studied using monoclonal antibodies (Mabs) specific to bovine B and T lymphocytes: BAQ155A (B), CH128A (BoCD2), CACT138A (BoCD4), CACT80 (BoCD8), BAQ4A (Null cells). Topographical distribution of the HN T and B cell subset appears similar to the distributions in the LN. The germinal centres contained B+, BoCD2+ and BoCD4+ cells, whereas no staining of lymphocytes could be seen in the mantle zone. BoCD2+, BoCD4+ and BoCD8+ lymphocytes were located in the parafollicular lymphatic tissue, whereas B and Null lymphocytes were scattered. The same pattern was observed in the hyperplastic haemolymphadenitis of steers with respiratory diseases with an increased positive staining for BoCD4 and BoCD8. A similar pattern was observed for HN and LN Immunoglobulin Containing Cells (ICC). Furthermore, in the calf HN, IgM positive ICC were the most frequent class (44% in HN vs. 33% in LN). It is likely that they could contribute to produce a particularly efficient primary immune response. This is the first study of the distribution of different lymphocyte phenotypes in mammalian haemolymph nodes.

Animals↗

Intrathoracic sources of caudal mediastinal lymph node efferent lymph in sheep.

We investigated the intrathoracic contributions to the caudal mediastinal lymph node (CMN) efferent lymph in 12 anesthetized sheep after removing possible systemic contributions from below the diaphragm. We interrupted various pathways that may send lymph to the CMN (chest wall, esophagus, lung). Because the experiment is destructive, we did the resections in various combinations and waited 1 h between steps. Base-line CMN efferent lymph flow averaged 0.90 +/- 0.52 g/15 min (mean +/- SD). Cutting the pulmonary ligaments bilaterally caused lymph flow to decrease by an average of 58%. In five sheep, cauterizing around the lung hila reduced lymph flow by 16% of base line, cauterizing along the esophagus reduced lymph flow by 18% of base line, and cauterizing along the chest wall increased lymph flow by 6% of base line. After complete isolation of the node, except for the bronchoesophageal artery, dorsal mediastinal vein, and CMN efferent duct, 14% of base-line flow remained. The lymph-to-plasma total protein concentration ratios did not change significantly with any procedure. Under the conditions of our experiments, approximately 74% of base-line intrathoracic CMN efferent flow comes from the lung.

Abdominal Muscles↗

[Effects of radiation therapy for paraaortic lymph node involvement and recurrent lymph node metastases from gastric cancer].

Effects of radiation therapy for lymph node metastases from gastric cancer were retrospectively analyzed. The radiation sites were residual paraaortic lymph node involvement and postoperative recurrent lymph node metastases in 10 patients. The size of lymph node swelling was decreased in 6 (60%) patients after radiation therapy using liniac. Complaints due to lymph node metastases such as pain and edema of extremities were voiced by 7 patients. These complaints were eventually relieved or disappeared in all 7 patients. There were no severe adverse effects during radiation therapy, and 7 patients (70%) could shift to home care. One-year and 3-year survival rates were 20 and 10%, respectively. Radiation therapy for lymph node metastases from gastric cancer was chiefly effective in relieving complaints. Although it is unclear whether radiation therapy can improve the survival rate, these results suggest that radiation therapy could be one of the most useful locoregional therapies for paraaortic lymph node involvement and recurrent lymph node metastases from gastric cancer.

Aged↗

In vitro investigation of detectability of colorectal lymph nodes and diagnosis of lymph node metastasis in colorectal cancer using B-mode sonography.

PURPOSE: The aim of this in vitro study was to assess the feasibility of using high-frequency sonography to identify colorectal lymph nodes and to diagnose colorectal lymph node metastasis. METHODS: In part 1 of this study, resected colorectal tissues from 13 patients with colorectal cancer were scanned in a water bath using B-mode sonography performed at high frequency (10 MHz) to identify lymph nodes. The colorectal tissues were then carefully dissected to remove all lymph nodes. Detectability was calculated as the ratio of the number of sonographically detected nodes to the total number of histopathologically confirmed nodes. Student's t test was performed to compare sizes between these groups; a p value of less than 0.05 was considered significant. In part 2, 4 features of lymph nodes identified on B-mode sonography--size, shape, border, and echogenicity--and their combinations were evaluated for their ability to diagnose lymph node metastasis. Discriminant and receiver operating characteristic curve analyses were performed. RESULTS: In part 1, B-mode sonography performed in vitro detected 79 (48%) of the 165 histopathologically identified lymph nodes and 34 (87%) of the 39 histopathologically identified metastatic nodes. The mean size, or mean longest axis (+/- standard deviation), of the sonographically detected nodes (6.4 +/- 2.9 mm) was significantly larger than that of undetected nodes (3.6 +/- 1.7 mm; p < 0.01). In part 2, the most effective feature distinguishing metastatic from nonmetastatic lymph nodes was echogenicity, followed by size, shape, and border. However, a combination of at least 2 features (eg, echogenicity and size) provided better distinction of nodes than did any 1 feature. In the receiver operating characteristic curve of the 4-feature combination, an increase in sensitivity is accompanied by a decrease in specificity: at a sensitivity of 100%, specificities decreased to 60% or less. However, even with the optimal combination of features, the sensitivity and specificity did not both reach 85% at any operating point. CONCLUSIONS: The results of this node-by-node in vitro study show the current limitations and potential of sonography for assessing colorectal lymph nodes. High-frequency sonography may be insufficient for identifying lymph node metastasis in colorectal cancer.

Adenocarcinoma↗

Intraoperative, radio-guided sentinel lymph node mapping in laparoscopic lymph node dissection for Stage I testicular carcinoma.

BACKGROUND: The management of regional lymph nodes in patients with clinical Stage I testicular carcinoma is a controversial problem. The authors investigated the feasibility and accuracy of radio-guided mapping of sentinel lymph nodes (SLNs) for men with clinical Stage I testicular tumors. METHODS: Twenty-two patients with clinical Stage I testicular carcinoma were enrolled in the study. One day before surgery, (99m)Technetium-labeled phytate was injected around the testicular tumor. After undergoing radical orchiectomy, patients underwent laparoscopic retroperitoneal lymph node dissection (L-RPLND). All radioactive lymph nodes were marked in the L-RPLND procedure, and three-dimensional SLN maps were made. All resected lymph nodes were evaluated by routine histopathologic examination, and the clinical significance of intraoperative SLN mapping was evaluated. RESULTS: SLNs were detected in 21 of 22 patients (95%). Nearly all SLNs were detected at the ventral or lateral side of the vena cava or at the aorta between the levels of the aortic bifurcation. All SLNs were detected easily in a surgical procedure. Only 1 radio-positive area per patient was identified in 15 patients, and approximately 2-4 positive areas were detected in 6 patients. Two patients had micrometastasis only in SLNs. In 2 patients who had seminoma, lymph node recurrences (at the level of the renal vein and in the obturator lymph node area) occurred at 10 months and 20 months after surgery. CONCLUSIONS: Radio-guided mapping of SLNs with laparoscopy was feasible, and nearly all SLNs were detected accurately by the procedure. In the near future, the standard retroperitoneal lymph node dissection may be avoided in most patients with clinical Stage I testicular carcinoma by utilizing focused examination of SLNs.

Adult↗

Morbidity following sentinel lymph node biopsy versus axillary lymph node dissection for patients with breast carcinoma.

BACKGROUND: Axillary lymph node dissection for staging the axilla in breast carcinoma patients is associated with considerable morbidity, such as edema of the arm, pain, sensory disturbances, impairment of arm mobility, and shoulder stiffness. Sentinel lymph node biopsy electively removes the first lymph node, which gets the drainage from the tumor and should therefore be associated with nearly zero morbidity. METHODS: Postoperative morbidity (increase in arm circumference, subjective lymphedema, pain, numbness, effect on arm strength and mobility, and stiffness) of the operated arm was prospectively compared in 35 breast carcinoma patients after axillary lymph node dissection (ALND) of Level I and II and 35 patients following sentinel lymph node (SN) biopsy. RESULTS: Patient characteristics were comparable between the two groups. Postoperative follow-up was 15.4 months (range, 4-28 months) in the SN group and 17.0 months (range, 4-28 months) in the ALND group. Following axillary dissection, patients showed a significant increase in upper and forearm circumference of the operated arm compared with the SN patients, as well as a significantly higher rate of subjective lymphedema, pain, numbness, and motion restriction. No difference between the two groups was found regarding arm stiffness or arm strength, nor did the type of surgery affect daily living. CONCLUSIONS: SN biopsy is associated with negligible morbidity compared with complete axillary lymph node dissection.

Activities of Daily Living↗

Recombinant bovine interferon-alpha I 1 inhibits the migration of lymphocytes from lymph nodes but not into lymph nodes.

Recombinant bovine interferon-alpha I 1 (IFN-alpha) was tested for effects on lymphocyte migration into and out of the lymph nodes of sheep. Chronic lymph drainage methods were used to monitor the efferent lymph of single lymph nodes of unanaesthetized animals. When IFN-alpha was injected into the drainage area of the lymph node, infused directly via an afferent lymphatic, or injected intravenously, a marked decrease in cell output was observed. Nanogram quantities of IFN-alpha produced an effect that lasted several hours. To test whether this effect was specific for lymphocytes, we first stimulated a lymph node with Staphylococcus aureus so that large numbers of neutrophils and lymphocytes were present in efferent lymph. When IFN-alpha was then injected, the lymphocytes disappeared from efferent lymph but the neutrophils did not. Normal efferent lymph cells were labeled with radioisotopes and injected intravenously during the IFN-alpha induced effect. The entry of lymphocytes from the blood was significantly enhanced at a time coinciding with the suppressed cell exit in the efferent lymph. Recovery data indicated that the lymphocytes were retained temporarily in the lymph node but were not destroyed. Furthermore, the bovine IFN-alpha does not appear to be conspicuously antigenic in sheep. It is not yet certain whether IFN-alpha enhances the interactions of cells within the lymph node thereby potentiating immunologic reactions.

Animals↗

The influence of serial sections, immunohistochemistry, and extension of pelvic lymph node dissection on the lymph node status in clinically localized prostate cancer.

OBJECTIVES: Pelvic lymph node metastases indicate a poor prognosis for patients with clinically localized prostate cancer. The aim of the study was to investigate the value of extended histopathological techniques considering the extent of pelvic lymphadenectomy and preoperative risk factors. METHODS: Total of 194 patients with prostate cancer were examined. At first all patients had a sampling of the sentinel lymph nodes (SLN) followed in most cases by a modified or extended pelvic lymphadenectomy. Step sections, serial sections and immunohistochemistry (IHC, pancytokeratin antibody) were analyzed in all SLN and so-called non-SLN of the first 100 patients. Later serial sections and IHC of non-SLN were left out. RESULTS: In 26.8% lymphatic metastases were found. The detection rate of lymph node-positive patients depend significantly on the chosen extension of pelvic lymphadenectomy. Limiting the histopathological investigation to the lymph node specimen of the obturator fossa only 44.2% of lymph node-positive cases would have been identified. An additional inclusion of all lymph nodes surrounding the external iliac vessels improves the sensitivity to 65.4% (46.7% and 73.3% for the first 100 patients). Compared to the extension of pelvic lymphadenectomy the diagnostic gain of serial section and IHC (13.8% versus 53.3%) was comparably low. CONCLUSIONS: The extension of pelvic lymph node dissection is of outstanding value for the identification of node-positive patients. Limiting the number of lymph nodes to the ones with the highest probability of bearing lymphatic spread (SLN) makes the use of extensive histopathological techniques more feasible.

Humans↗