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Patterns of lymphatic spread in rectal cancer. A topographical analysis on lymph node metastases.

The presence of lymph node (LN) metastases is the most important prognostic factor in rectal cancer. The exact LN status can only be known when an extended lymph node dissection (LND) has been performed, a process not routinely performed. If the likelihood of LN metastases can be more accurately assessed preoperatively, then an optimal multimodality treatment plan can be established. 605 patients with primary rectal cancer operated upon with wide LND (D3 level) were analysed for LN metastases combining topographical localisation and morphological features of the tumour. More distal rectal tumours tend to more LN metastases and more lateral lymphatic spread. Tumours >or=3 cm show more LN metastases compared with those smaller than 3 cm. Depth of bowel wall invasion is strongly related to the presence of LN metastases. The peritoneal reflection has no discriminating role in the mode of spread. Intra-operative assessment by the surgeon for presence of LN metastases is not reliable. When localisation, depth of bowel wall invasion and diameter of a rectal tumour are known, a likelihood of LN metastases can be assessed pre-operatively, not intra-operatively.

Humans↗

[Clinical pathology feature and prognostic factors of cervical lymph node metastases in hypopharyngeal carcinoma].

OBJECTIVE: To investigate the risk clinicopathological factors of primary tumor in the prediction of cervical lymph node metastases and the cervical lymph node prognostic factors in hypopharyngeal squamous cell carcinoma. METHODS: A retrospective study was carried out to review the histopathological data from 98 hypopharyngeal squamous cell carcinoma patients. The relationship between histopathological parameters and cervical lymph node metastases were evaluated by means of a univariate chi2 test and multivariate stepwise logistic regression model. And the Cox regression model was used to define possible pathological parameters of neck node affecting survival including N staging, presence of cervical lymph node metastases and extracapsular nodal spread, size and number of positive neck nodes, and levels of positive neck nodes. RESULTS: The overall 5-year survival rate of patients with hypopharyngeal carcinoma was 28.6%. In a univariate and multivariate analysis, it was confirmed that size and growth pattern of primary tumor correlated to cervical lymph node metastases. In a multivariate Cox regression analysis, the most significant prognostic factors of cervical lymph node were the size of positive neck nodes and level involved. CONCLUSIONS: Cervical lymph node metastases were one of the most significant prognostic factors of hypopharyngeal carcinoma. The identification of patients at risk for cervical lymph node metastases and the management of the neck by coping with pathological factors of cervical lymph node affecting survival are very important to improve the treatment and prognosis of hypopharyngeal carcinoma.

Adult↗

Computed tomography and ultrasonography of metastatic cervical lymph nodes in oral squamous cell carcinoma.

OBJECTIVES: To define criteria for CT and US in differentiating cervical lymph node metastases in oral squamous cell carcinoma (SCC). MATERIALS AND METHODS: CT and/or US of 230 metastatic lymph nodes and 228 benign lymph nodes in 147 patients with oral SCC were retrospectively evaluated. The CT and US findings of each lymph node were compared with the histopathological findings. A metastasis was defined on CT as a lymph node with rim or heterogeneous enhancement, or measuring 10 mm or more in the short axis, regardless of enhancement pattern, and on US as having definite internal echoes, regardless of size, or without definite internal or hilar echoes, but measuring 10 mm or more in the short axis. A lymph node with hilar echoes or a ratio of the long to short axis (L/S ratio) of 3.5 or more was considered benign. A lymph node failing to comform to any of these categories was termed questionable. RESULTS: The positive predictive value (PPV) for CT was 90.8% and the negative predictive value (NPV) was 70.4%. However, 65.7% of all lymph nodes could not be classified as either metastastic or benign. PPV for US was 96.5% and NPV was 88.1%. 25.5% of all lymph nodes could not be classified as either metastatic or benign. CONCLUSIONS: Despite limitations in detecting metastases, by including a third category 'questionable' our criteria appear clinically more useful than other current methods based on two groups only.

Adult↗

[Lymph node excision in invasive Barrett carcinoma].

Similar to squamous cell esophageal cancer, the lymph node status constitutes the major prognostic factor after complete tumor resection (R0-resection) in patients with adenocarcinoma of the distal esophagus (the so-called Barrett's cancer). Lymphatic spread in patients with Barrett's cancer, however, appears to follow certain rules. Lymphatic spread is closely correlated to the pT-category of the primary tumor, starts only after infiltration of the submucosa und is initially limited to the regional lymph nodes. Distant lymph node metastases are almost exclusively found in patients with multiple positive regional nodes, skipping of regional lymph nodes is rare. These observations set the stage for tailored lymphadenectomy-strategies based on the, sentinel-lymphadenectomy' concept.

Adenocarcinoma↗

The B cell is the initiating antigen-presenting cell in peripheral lymph nodes.

We have examined the role of B cells in antigen presentation in lymph nodes in several ways. We found that mice depleted of B lymphocytes via chronic injection of anti-mu-chain antibody do not mount peripheral lymph node T cell proliferative responses to normally immunogenic doses of antigen. Depletion of B cells by passage of immune lymph node cells over anti-immunoglobulin columns early after immunization depletes antigen-presenting function from draining lymph nodes, and this function can be restored by using B cells or splenic adherent cells to allow the remaining T cells to proliferate. Lymph node B cells present antigen very effectively to lines of antigen-specific T cells. However, unfractionated lymph node cells from anti-mu-treated mice present very poorly, if at all, whereas unfractionated spleen cells from the same mice do present antigen. This is in keeping with our previous finding that helper T cell function in the spleen is normal in B cell-deprived mice. Finally, when mice homozygous for the lymphoproliferative gene lpr are treated chronically with anti-mu-chain antibody, lymphadenopathy is greatly retarded, suggesting a role for B cells in the massive proliferation of T cells in this syndrome. From this analysis, it would appear that the initiating antigen-presenting cell in the lymph node is a B lymphocyte, and that B lymphocytes in lymph nodes may be distinct from those in the spleen. It is of interest that these results also suggest that the lymph node lacks an antigen-presenting cell that is found in the spleen, perhaps the dendritic cell.

Animals↗

Sentinel lymph node biopsy and melanoma biology.

Minimally invasive intraoperative lymphatic mapping and sentinel node biopsy has become the standard approach for staging the regional lymph nodes for early-stage melanoma. The procedure requires close collaboration of surgeon, pathologist, and nuclear medicine physician. The strength of lymphatic mapping and sentinel node biopsy is its accuracy of detecting occult lymph node metastases. Reverse transcriptase-PCR (RT-PCR) analyses of either fresh-frozen or paraffin-embedded sections of the sentinel lymph nodes have been found to be more sensitive than H&E staining or immunohistochemistry techniques, but lack of specificity and limits in the availability of tissue specimens make this technique impractical for routine use. Three randomized clinical trials are examining the therapeutic value of lymphatic mapping and sentinel node biopsy for melanoma. Preliminary results of the Multicenter Lymphadenectomy Trial I show the high level of accuracy and low morbidity of lymphatic mapping and sentinel node biopsy done through an international working group. The therapeutic value of lymphatic mapping and sentinel node biopsy is still unclear. Multicenter Lymphadenectomy Trial II will test the clinical significance of lymph nodes evaluated by RT-PCR and the value of completion lymph node dissection for patients found to have tumor-positive sentinel lymph nodes by H&E, immunohistochemistry, or RT-PCR. The Sunbelt Melanoma Trial examines the therapeutic value of completion dissection and benefits of Intron A. The ability to detect occult nodal metastases and evaluate the interaction of primary tumor with the regional lymph nodes may provide for better understanding of the metastatic process in patients with melanoma and help to determine the function of the regional lymph nodes as markers of metastases or incubators of tumor cells in the metastatic cascade.

Humans↗

Preoperative diagnosis of lymph node metastases in gastric cancer by magnetic resonance imaging with ferumoxtran-10.

BACKGROUND: Knowledge regarding the presence and location of lymph node metastasis in gastric cancer is essential in deciding on the operative approach. Lymph node metastases have been diagnosed with imaging tests such as computed tomography (CT) and ultrasonography (US); however, the accuracy of such diagnoses, based on size and shape criteria, has not been adequate. Ferumoxtran-10 (Combidex; Advanced Magnetics) is a lymphotropic contrast agent for magnetic resonance imaging (MRI) whose efficacy for the detection of metastatic lymph nodes in various cancers has been reported by several investigators; however, its efficacy for this purpose has not been reported for gastric cancer. We investigated the efficacy of ferumoxtran-10-enhanced MRI for the diagnosis of metastases to lymph nodes in gastric cancer. METHODS: Seventeen consecutive patients who were diagnosed with a nonearly stage of gastric cancer were enrolled in the study. All the patients were examined by MRI (Signa Horizon 1.5 T; GE Medical; T2*-weighted images) before and 24 h after the intravenous administration of ultrasmall particles of superparamagnetic iron oxide--ferumoxtran-10 (2.6 mg Fe/kg of body weight)--and the presence or absence of metastasis was determined from the enhancement patterns. The imaging results were compared with the corresponding histopathological findings following surgery. RESULTS: Of 781 lymph nodes dissected during surgery, the imaging results of 194 nodes could be correlated with their histopathological findings. Fifty-nine lymph nodes from 11 patients had histopathological metastases. In nonaffected normal lymph nodes, we observed dark signal intensity on MRI caused by the diffuse uptake of the contrast medium by macrophages resident in the lymph nodes, which phagocytose the iron oxide particles of ferumoxtran-10. The number of phagocytic macrophages was decreased in metastatic lymph nodes, and they showed various patterns of decreased uptake of ferumoxtran-10. Three enhancement patterns were observed in lymph nodes: (A) lymph nodes with overall dark signal intensity due to the diffuse uptake of ferumoxtran-10; (B) lymph nodes with partial high signal intensity due to partial uptake; and (C) no blackening of lymph nodes due to no uptake of ferumoxtran-10. Patterns (B) and (C) were defined as metastatic. The sensitivity, specificity, positive predictive value, negative predictive value, and overall predictive accuracy of postcontrast MRI were 100% (59/59), 92.6% (125/135), 85.5% (59/69), 100% (125/125), and 94.8% (184/194), respectively. These parameters for predictive accuracy were much superior to these parameters previously evaluated by CT or US. Nodes in the retroperitoneal and paraaortic regions were more readily identified and diagnosed on the MR images than those in the perigastric region. CONCLUSION: The present study confirmed that ferumoxtran-10-enhanced MRI is useful in the diagnosis of metastatic lymph nodes and that the use of this modality will be helpful in treatment decision-making for gastric cancer patients.

Adult↗

[Microinvasive ductal carcinoma of the breast. Role of axillary lymph node dissection].

The role of axillary lymph node dissection for microinvasive ductal carcinoma in situ of the breast was analyzed in a series of 60 consecutive cases. Forty-four cases were subclinical mammographically-detected carcinomas revealed by the clusters of microcalcifications. Although pathologists differ in their criteria for microinvasion, the maximal size considered in this retrospective study was 2 mm. Axillary lymph node involvement was found in 3 cases (i.e. 5%) which harbored poor histologic features: comedocarcinoma subtype, high nuclear grade, and size of the ductal carcinoma in situ greater than 3 cm, requiring total mastectomy. While there is no need for axillary dissection in women with pure ductal carcinoma in situ, the management is quite different in proven microinvasion. Owing to the weakness of prognostic information given by cellular, biochemical and molecular features, instead of lymph node status, axillary dissection is still recommended in microinvasive ductal carcinoma in situ.

Adult↗

Evaluation of retroperitoneal and pelvic lymph node metastases with MRI and MR lymphangiography.

Local, regional lymph node involvement is an essential prognostic factor and an important determinant of treatment choices for patients with retroperitoneal and pelvic cancer. Current cross-sectional imaging modalities, including computed tomography and magnetic resonance (MR) imaging, use the nonspecific criterion of size and are limited in their ability to differentiate benign from malignant lymph nodes. MR lymphography is a promising imaging modality in differentiating benign from metastatic lymph nodes and provides information on lymph node morphology and function. Ultrasmall superparamagnetic iron oxide (USPIO) particles with a long plasma circulation time are suitable as an MR contrast agent for intravenous MR lymphography. They are taken up by macrophages in normally functioning nodes and reduce the signal intensity of tissue in which they accumulate because of T2 and susceptibility effects of iron oxide. In metastatic nodes, macrophages are replaced by cancer cells, which lack reticuloendothelial activity and cannot take up USPIO. The main mechanisms that might explain a heterogeneous node appearance after USPIO injection are discussed. In published reports, USPIO has shown high degrees of sensitivity and specificity for characterizing lymph nodes in cancer patients. We review the development of USPIO compounds, their imaging characteristics, and our clinical experience.

Contrast Media↗

Effects of anchorage-modulating doses of concanavalin A, microtubule-disrupting drugs and microfilament perturbants, cytochalasins, on the phosphatidylinositol response of rat lymph-node cells.

In lymphocytes isolated from rat lymph nodes, concanavalin A stimulated the 32PO4 incorporation into phosphatidylinositol and phosphatidic acid in a dose-dependent manner up to 200 micrograms of the lectin per ml of the lymphocyte culture. [3H]Thymidine incorporation was found to be optimal at 2 micrograms concanavalin A per ml of the culture when the incorporation was examined at the same cell density as was used in the determination of the 32PO4 incorporation. As previously described (Wang, J.L. and Edelman, G.M. (1978) J. Biol. Chem. 253, 3000-3007), the [3H]thymidine incorporation was inhibited at doses higher than 5 micrograms/ml in a dose-dependent manner. These results indicate that concanavalin A produced the phosphatidylinositol PI response of rat lymph-node cells in the dose range in which the mobility and distribution of lymphocyte surface receptors were modulated by the lectin (Yahara, I. and Edelman, G.M. (1972) Proc. Natl. Acad. Sci. U.S.A. 69, 608--612). Colchicine and vinblastine at a concentration of 10(-4) M did not inhibit the concanavalin A-induced PI response of rat lymph-node cells. Cytochalasins B and D at a concentration of 10(-5) M enhanced the concanavalin A-induced PI response to some degree. All the results obtained suggest that submembranous assemblies of microtubules and microfilaments do not play an indispensable role in the sequence of events involved in the PI response of rat lymph-node cells.

Animals↗

Sentinel lymph node radiolocalization in head and neck squamous cell carcinoma.

OBJECTIVES: To determine the feasibility of sentinel node radiolocalization in stage N0 in head and neck squamous cell carcinoma and to gain insight as to whether the sentinel node could be prognostic of regional micrometastatic disease. STUDY DESIGN: A prospective report on the application sentinel node radiolocalization in eight patients with N0 squamous cell carcinoma of the head and neck region. METHODS: For each patient a peritumoral submucosal injection of filtered technetium (99mTc) prepared with sulfur colloid was performed immediately following intubation. After at least 30 minutes, focal areas of accumulation corresponding to a sentinel node were marked on the skin surface. Complete neck dissections were performed, and the sentinel nodes were identified for later histological evaluation and comparison to the remaining lymphadenectomy specimen. RESULTS: Sentinel node radiolocalization accurately identified two or more sentinel lymph nodes in all eight cases. In one patient, two of the three lymph nodes containing micrometastatic disease were sentinel lymph nodes. There was no instance in which sentinel node was negative for micrometastatic disease while being positive in a nonsentinel lymph node. CONCLUSIONS: Accurate localization of the sentinel lymph node using radiolabeled sulfur-colloid is feasible in patients with squamous cell carcinoma of the head and neck region. Although sentinel node radiolocalization in head and neck squamous cell cancer may potentially reduce the time, cost, and morbidity of regional lymph node management, more experience with technique is required before its role can be determined.

Aged↗

The optimal number of sentinel lymph nodes for focused pathologic examination.

The sentinel lymph node (SLN) procedure provides an alternative method for assessing the axillary lymph nodes in patients with breast cancer. The SLN is typically subjected to a focused pathologic examination involving the examination of multiple tissue levels and/or keratin immunohistology. The number of SLNs submitted may vary widely, in some cases rivaling that of a complete axillary dissection (CAD). We examined our experience over the last 2 years in order to determine the optimal number of SLNs for focused pathologic evaluation. All SLN cases for the years 2000 and 2001 were retrieved from the files of the Pathology Department at Magee-Womens Hospital and were tabulated to determine the average number of SLNs per case, the number of SLNs submitted, the actual SLN that was positive for each case, the type of metastasis, and the average number of SLNs per case for each surgeon. There were 662 operative cases that yielded 1576 SLN accessions and 1758 total SLNs. The range of SLNs submitted was 1 to 11. Overall there was a mean of 2.4 SLNs accessioned per case and a mean of 2.7 SLNs per case. A study of the statistics of SLNs submitted by seven surgeons yielded two distinct groups, with one group submitting virtually all of the cases where there were consistently more than four SLNs per case. Ninety-seven percent of positive SLNs were discovered in the first three SLNs submitted, regardless of surgeon identity. The SLNs beyond numbers one to three yielded positive results by keratin in only four cases. Focused pathologic examination of SLNs was most effective for the first three SLNs submitted for any given case. The variation in the number of SLNs submitted per case was different based upon the different practice patterns of surgeons. It is suggested that for more than three SLNs submitted, simple routine lymph node examination would be appropriate.

Breast Neoplasms↗

Most important lymph node information in gastric cancer: multivariate prognostic study.

BACKGROUND: In gastric cancer, the level and number of lymph node metastases is useful for predicting survival, and there are several staging systems for lymph node metastasis. The aim of this study was to compare the several lymph node classifications and to clarify the most important lymph node information associated with prognosis using multivariate analysis. METHODS: A total of 106 patients with histologically node-positive gastric cancer treated by radical gastrectomy and extended lymph node dissection (D2, D3) were studied. The level of lymph node metastasis was categorized simply as Level I nodes (perigastric, No.1-6), Level II nodes (intermediate, No.7-9), and Level III nodes (distant, No.10-16), irrespective of the tumor location. The Level II nodes included lymph nodes along the left gastric artery, common hepatic artery, and celiac trunk. RESULTS: Overall 5-year survival rate was 51%. Univariate analysis showed that 5-year survival rate was significantly influenced by the level of positive nodes (P < .01), total number of positive nodes (P < .01), number of positive Level I nodes (P < .01), and number of positive Level II nodes (P < .01), in addition to the tumor location (P < .05), tumor size (P < .05), gross type (P < .01), and depth of wall invasion (P < .01). Of these, independent prognostic factors associated with 5-year survival rate were the number of positive Level II nodes (0-1 vs. > or =2) (62% vs. 19%, P < .01) and the depth of wall invasion (within vs. beyond muscularis) (79% vs. 43%, P < .01). CONCLUSIONS: Among several staging systems for lymph node metastases, the number of positive Level II nodes provided the most powerful prognostic information in patients with node-positive gastric cancer. When there were two or more metastases in the Level II nodes, prognosis was poor even after D2 or D3 gastrectomy.

Adult↗

Differentiated thyroid cancer: a stage adapted approach to the treatment of regional lymph node metastases.

The controversy in the management of regional lymph nodes in patients with differentiated thyroid cancer is discussed on the basis of a review of the literature. Since no prospective studies have yet compared limited dissections ('node picking') with more extensive dissections [(modified) radical neck dissection], a retrospective analysis was performed using two patient groups in which patients were managed differently with regard to the preoperative diagnosis and treatment of regional lymph node metastases. Only patients with proven lymph node metastases were included in the study. Because of selection methods necessary to create comparable patient groups, only 83 patients could be included in the analysis. There was no difference in survival or recurrence rate in either group, although recurrences occurred less frequently in the explored side of the neck after MRND (3.9% vs. 6.3%). More postoperative morbidity was found in the patients who had been subjected to a more extensive search for and treatment of lymph node metastases. Because of the relatively small number of patients only the difference in occurrence of accessory nerve palsies reached statistical significance (P = 0.05). It is advocated that only in the case of papillary carcinoma with limited lymph node involvement node picking is the procedure of choice. In all other cases a modified radical neck dissection should be standard treatment.

Female↗

Sentinel lymph node biopsy in breast cancer.

The sentinel lymph node (SLN) procedure consists of identifying the first lymph node to receive lymphatic vessels draining a tumour. Sentinel node biopsy is a minimally invasive technique, resulting in lower morbidity than traditional axillary lymph node dissection. Screen detected breast cancers are associated with approximately a 20% incidence of axillary node involvement. Sentinel node biopsy represents a minimally invasive method of accurately staging these patients.

Breast Neoplasms↗

Lymph-node metastases in patients with melanoma: what is the optimum management?

Lymph-node metastasis is an indicator of poor prognosis for patients with melanoma. The management of regional nodes is controversial, with continuing debate about whether surgery or radiotherapy of positive lymph nodes improves long-term survival or whether nodal involvement is merely a marker of aggressive disease. However, there is general agreement that systemic chemotherapy is rarely an effective form of management. This review therefore considers surgical and radiotherapeutic aspects of lymph-node management in patients with melanoma. We discuss regional control and survival after lymph-node surgery in retrospective series, randomised trials of elective lymph-node dissection, the role of 'sentinel' lymph-node biopsy, radiobiology and radiotherapy fractionation issues in melanoma treatment, retrospective studies of adjuvant nodal radiotherapy, and finally, randomised trials of adjuvant radiotherapy after lymph-node dissection.

Combined Modality Therapy↗

Equivalent cross relaxation rate image for decreasing a false negative case of sentinel lymph node biopsy.

In the breast carcinamas, sentinel lymph node biopsy (SLNB) attracts attention as technique to be settled by axillary lymph node metastasis, but existence of a false negative case is a problem. Equivalent cross relaxation rate image (ECRI) is the measurement method that we can evaluate a change of organization structure quantitatively by magnetic resonance imaging. We executed axillary ECRI as a purpose with decreasing a false negative case of SLNB. ECRI related to a macroscopic image, and it was possible to evaluate yes or no of axillary lymph node metastasis. ECRI is the useful method to evaluate adaptability of SLNB.

Axilla↗

Staging of gastric cancer: correlation of lymph node size and metastatic infiltration.

OBJECTIVE: The assessment of lymphatic metastases is an important factor in the staging of gastric cancer. Lymph node size has been used as one criterion for possible nodal metastasis. Although enlarged regional lymph nodes are generally interpreted as metastases, few data are available that correlate lymph node size with metastatic infiltration. MATERIALS AND METHODS: In a prospective morphometric study, the regional lymph nodes from 31 gastrectomy specimens of consecutive patients with primary gastric adenocarcinoma were analyzed. The lymph nodes were counted, the largest diameter of each node was measured, and each node was analyzed for metastatic involvement by histologic examination. The frequency of metastatic involvement was calculated and correlated to lymph node size. RESULTS: A total of 1253 lymph nodes were present in the 31 specimens examined for this study. A mean number of 40 lymph nodes (range, 20-53) were found in each specimen. Of these 1253 nodes, 922 (74%) were tumor-free and 331 (26%) contained metastases. The mean diameter of the lymph nodes free of metastases was 4.1 mm, whereas that of nodes infiltrated by metastases was 6.0 mm (p < .0001). Of the tumor-free lymph nodes, 735 (80%) were less than 5 mm in diameter, whereas 182 (55%) nodes containing metastases were less than 5 mm in diameter. Of the 10 patients without lymph node metastases, seven had at least one node that was 10 mm or greater in diameter; similarly, 15 (71%) of the 21 patients with node metastases had at least one node that was 10 mm or greater in diameter. CONCLUSION: Lymph node size is not a reliable indicator for lymph node metastasis in patients with gastric cancer.

Adenocarcinoma↗