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[Limitations of sentinel lymph node biopsy in breast cancer].

Sentinel lymph node biopsy is a widely accepted new surgical procedure in the treatment of early breast cancer. However, not only numerous details of the technique, but also limitations of the method, such as maximal tumor size, multifocal disease, accuracy following neoadjuvant chemotherapy and appropriateness in ductal carcinoma in situ are being debated. Recent multicenter studies could establish the lower morbidity of sentinel lymph node biopsy compared to axillary clearance as well as the false-negative rate which lies between 7 and 9.7%. In unifocal T1 disease with clinically negative axillary lymph nodes, the method is considered to be standard of care. Evidence is growing that it may also be appropriate in larger and multifocal tumors while the method is unreliable after neoadjuvant chemotherapy.

Breast Neoplasms↗

Ki-1-positive anaplastic large cell lymphoma with different phenotypes in skin nodules and lymph nodes.

A 54-year-old man had lymph node swelling and skin nodules. Neoplastic cells with pleomorphic nuclei, prominent eosinophilic nucleoli and abundant cytoplasm were present in the lymph node sinuses and around the dermal appendages. Neoplastic cells in the lymph nodes expressed Ber-H2 (CD30)+/KP1 (CD68)+/MAC387-/LN-5+. Those in the skin nodules expressed Ber-H2+/KP1-/MAC387+/LN-5-. These findings suggest that he had Ki-1-positive anaplastic large cell lymphoma (ALCL) with different phenotypes in lymph nodes and skin nodules. The discrepancy among KP1, MAC387 and LN-5 reactivities may represent the concurrent occurrence of ALCL and lymphomatoid papulosis. However, the possibility cannot be ruled out that ALCL developed first in the lymph nodes and then metastasized to the skin.

Antigens, CD↗

Reasoning with uncertainty in pathology: artificial neural networks and logistic regression as tools for prediction of lymph node status in breast cancer patients.

Axillary lymph node status is an important prognostic feature for patients with breast cancer, but the therapeutic value of axillary lymphadenectomy is controversial. It would be useful to be able to predict the status of axillary lymph nodes before lymphadenectomy from prognostic features evaluated in a previous breast biopsy. This prediction would be useful to optimize the treatment of patients with breast cancer who are unlikely to have nodal metastases. We studied 279 patients with invasive breast carcinoma treated with modified radical mastectomy or with lumpectomy combined with axillary lymph node dissection. Prognostic factors evaluated were age, histologic type of invasive tumor, presence of associated ductal and/or lobular carcinoma in situ, lesion size, histologic and nuclear grades, DNA index, presence of multiploidy by flow cytometric analysis, and immunocytochemical expression of estrogen and progesterone receptors, proliferating nuclear cell antigen, and HER-2/neu oncogene. Several probabilistic neural networks (NNs) with genetic algorithms were developed using prognostic features as input neurons and lymph node status (positive or negative) as output neurons. The data were also studied with multiple regression and logistic regression analysis. The best NN model trained with 224 cases using 19 input neurons. It classified correctly 49 (89.0%) of 55 unknown cases (specificity, 97.2%; sensitivity, 80.0%; positive predictive value, 93.8%; negative predictive value, 87.5%). Several statistically significant models could be fitted with both multiple regression and logistic regression. The logistic regression model fitted with 240 cases using 6 independent variables estimated correctly 26 (66%) of 39 holdout cases. NNs and logistic regression models offer potentially useful tools to estimate the status of axillary lymph nodes of breast cancer patients before axillary lymphadenectomy. Future prospective studies with larger groups of patients and perhaps better prognostic markers are needed before these predictive multivariate models become ready for clinical use.

Adult↗

Intraoperative localization of lymph node metastases with a replication-competent herpes simplex virus.

OBJECTIVES: Lymph node status is the most important prognostic factor determining recurrence and survival in patients with mesothelioma and other thoracic malignancies. Accurate localization of lymph node metastases is therefore necessary to improve selection of resectable and curable patients for surgical intervention. This study investigates the potential to identify lymph node metastases intraoperatively by using herpes-guided cancer cell-specific expression of green fluorescent protein. METHODS: After infection with NV1066, a herpes simplex virus carrying green fluorescent protein transgene, human mesothelioma cancer cell lines were assessed for cancer cell-specific infection, green fluorescent protein expression, viral replication, and cytotoxicity. Murine models of lymphatic metastasis were established by means of surgical implantation of cancer cells into the preauricular (drainage to cervical lymph nodes) and pleural (mediastinal and retroperitoneal lymph nodes) spaces of athymic mice. Fluorescent thoracoscopy, laparoscopy, and stereomicroscopy were used to localize lymph node metastases that were confirmed by means of immunohistochemistry. RESULTS: In vitro NV1066 infected, replicated (5- to 17,000-fold), and expressed green fluorescent protein in all cancer cells, even when infected at a low ratio of one viral plaque-forming unit per 100 tumor cells. In vivo NV1066 injected into primary tumors was able to locate and infect lymph node metastases producing green fluorescent protein that was visualized by means of fluorescent imaging. Histology confirmed lymphatic metastases, and immunohistochemistry confirmed viral presence in regions that expressed green fluorescent protein. CONCLUSIONS: Herpes virus-guided cancer cell-specific production of green fluorescent protein can facilitate accurate localization of lymph node metastases. Fluorescent filters that detect green fluorescent protein can be incorporated into operative scopes to precisely localize and biopsy lymph node metastases.

Animals↗

[Effect of extent of lymph node dissection on prognosis of esophageal cancer].

The lymph node metastasis of the esophageal cancer are located in three main regions such as neck (H), thoracic cavity (T) and abdominal cavity (B). We studied on the relation between the extent of lymph node dissection and prognosis, and that between the lymph node metastasis and prognosis in each region (H.T.B). The long-term survival among the cases with adequate dissection, especially with the adequate dissection in the thoracic region, was better than that among the cases without adequate dissection. Furthermore, adequately dissected cases got better survival compared to the cases without adequate dissection with post-operative prophylactic irradiation. However, in the prognosis of the esophageal carcinoma, hematogenous metastasis have to be taken into consideration as well as lymph node metastasis. Therefore, in order to improve the prognosis of esophageal cancer, it is indispensable to treat the multidisciplinary therapy with immunochemotherapy as well as complete lymph node dissection.

Combined Modality Therapy↗

[Risk factors for retroperitoneal lymph node metastasis in ovarian cancer].

The incidence and significant risk factors for retroperitoneal lymph node metastasis were investigated in 48 patients with primary epithelial ovarian cancer. Twenty-four (50.0%) of the 48 patients had para-aortic and/or pelvic lymph node metastases. In retroperitoneal lymphadenectomy at primary cytoreductive surgery, all patients with lymph node metastases were found to have both para-aortic and pelvic lymph node metastases. It is possible that the lymphatic extension, from the pelvic lymph node to the para-aortic lymph node, is one of the routes of retroperitoneal lymph node metastases in primary epithelial ovarian cancer. The incidence of lymph node metastases significantly increased with the spread of the abdominal tumor, peritoneal cytology, peritoneal metastasis, omental metastasis, involvement of both ovaries and poor histological grade. In the multiple analysis, the spread of the abdominal tumor, positive peritoneal cytology and poor histological grade were found to be the most important risk factors for retroperitoneal lymph node metastasis in ovarian cancer.

Cystadenocarcinoma, Serous↗

[Sentinel lymph node detection and clinical applications].

INTRODUCTION: The sentinel lymph node (SLN) procedure consists of finding the first lymph node encountered by lymphatic vessels draining a tumor. This technique identifies the SLN histological status, which is representative of all the other draining area lymph nodes' status. EXEGESIS: SLN identification requires the injection of a lymphatic tracer, which could be either a blue dye or radiolabeled particles, or both. Performing a lymphoscintigraphy, which identifies and quantitates SLNs is a possibility provided by the use of radiolabeled particles before a gamma probe guided search is performed intraoperatively. Finally, a specific histopathological methodology involving serial sections of the entire SLN and immunohistochemistry is also required. CONCLUSION: This technique is applicable to melanoma in which the SLN status might be a stronger prognostic factor than Breslow's thickness; to breast cancer in order to avoid full axillary lymph node dissection in patients with small tumors; and potentially to other carcinomas.

Breast Neoplasms↗

Distribution of estrogen and progesterone receptors on primary tumor and lymph nodes in individual patients with breast cancer.

Primary breast cancer tissue and lymph nodes were obtained from 55 patients, Histologically, 34 of these patients had positive and 21 negative lymph nodes. Estrogen receptors (ER) and progesterone receptors (PR) were determined by a dextran-coated charcoal assay. The tumor tissue was ER positive in 58% of the cases and PR positive in 34%. The malignant lymph nodes were ER positive in 56% and PR positive in 24%. ER in 14% and PR in 5% of the benign lymph nodes could be detected. The primary tumor tissue and the corresponding malignant lymph nodes showed an identical ER and PR status, i.e. both tumor sites were receptor positive or both receptor negative, in 68 and 74%, respectively. However, 21% of the patients had receptor-positive tumors but receptor-negative lymph nodes. Receptor-positive lymph nodes in combination with receptor-negative tumors occurred in only 11% for ER and 6% for PR. These data show that receptor-positive malignant lymph nodes mostly display the same receptors status as the corresponding primary tumor, whereas receptor-negative lymph nodes may be combined with receptor-positive tumors.

Breast Neoplasms↗

Contrast enhancement of pathologic lymph nodes demonstrated by computed tomography.

Enlarged mediastinal, retroperitoneal and pelvic lymph nodes are often difficult to differentiate from vascular structures. Contrast medium is therefore used to help to discriminate arteries and veins from lymph nodes. This study was undertaken to investigate the degree to which pathologic lymph nodes become enhanced after an intravenous bolus injection of contrast medium. Computed tomography was performed in 25 patients with enlargement of retroperitoneal lymph nodes due to primary lympho-proliferative disease or metastases. A dynamic sequence of a well delineated lymph node was obtained over a period of two minutes. Contrast enhancement was seen in all lymph nodes, but of varying degree. The enhancement was correlated to that observed in the inferior vena cava. Most examined lymph nodes showed slight or moderate enhancement, but in five instances strong enhancement, more than 75 per cent of that of the vena cava, was found. These nodes could possibly have been misinterpreted as blood vessels.

Adult↗

[Cervical lymph node surgery in differentiated thyroid cancer: selective or elective lymphadenectomy?].

The value and prognostic significance of regional lymph node dissection in patients with thyroid cancer remains a matter of controversy. The classification of the cervical lymph nodes and the extent of their resection in patients with different thyroid cancers is also discussed. The aim of the paper was to present the space classification of regional lymph nodes, the incidence of their involvement and the extent of their resection in patients with differentiated thyroid cancer. The results of multicenter studies have indicated that regional lymph node metastases in patients with differentiated thyroid cancer, especially of a papillary type, have been frequent. Ipsilateral central, ipsilateral lateral, contralateral lateral, and mediastinal lymph nodes have been affected in 42-86%, 32-68%, 12-24%, and 3-20% of patients respectively. In 20% of patients only central lymph nodes have been affected, whereas in others metastases have been determined at least in 2 or more lymph node groups. Regional lymph nodes have been classified into Groups I-IV. Moreover, lymph node recurrences have been more frequent in patients who either have not got the regional lymph nodes removed or have only enlarged ones determined as involved excised. Therefore, primary regional lymph nodes dissection is indicated. Elective resection of the lymph nodes of Group I (central lymph nodes) as a part of primary total thyroidectomy in patients with thyroid cancer and more selective excision of the lymph nodes of Groups II-IV are recommended. The author has presented his own experience in lymph node dissection in patients with differentiated thyroid cancer and compared it with other results.

Humans↗

Outcome of patients with proximal gastric cancer depends on extent of resection and number of resected lymph nodes.

BACKGROUND: Studies have shown that the survival of patients with gastric adenocarcinoma is related to the number of regional lymph nodes with metastases. The probability of identifying node-positive cancers increases with the number of lymph nodes resected and examined. It has been recommended that at least 15 lymph nodes be removed and examined for adequate staging. Prospective randomized studies have shown the lymph node yield is much greater with the D2 resection than the D1. This study evaluated the relative contribution of both the number of resected lymph nodes and the extent of gastric resection (D1/D2) on the outcome of patients with proximal gastric cancer. METHODS: The medical records of 114 patients with adenocarcinoma of the proximal stomach, who underwent a curative gastric resection, were reviewed. Patients were stratified into four groups, i.e., two groups, D1/D1.5 and D2/D2.5, based on the extent of resection, and two groups based on the number of lymph nodes removed, fewer than 15 lymph nodes and 15 or more lymph nodes. Survival was determined by the method of Kaplan-Meier and differences compared by the log-rank test. Multivariate analysis was performed by using the Cox model. RESULTS: The number of resected lymph nodes had no effect on the survival of the group as a whole. A significant improvement in survival was noted for patients with a D2 or greater resection. The median survival of patients with 15 or more lymph nodes resected improved from 25 months to 42 months when treated with an extended resection, (D2 or D2.5). Resection of 15 or more lymph nodes alone, or combined with an extended resection, resulted in a statistically significant improvement in survival for patients in American Joint Committee on Cancer Staging (AJCC) stage II. CONCLUSIONS: Both resection of 15 or more lymph nodes and extended lymphadenectomy contributed to the survival advantage observed in patients with AJCC stage II gastric cancer. The D2 gastric resection prolonged the median survival time and improved the 5-year survival rate for patients with 15 or more resected lymph nodes.

Adenocarcinoma↗

Computer-assisted analysis of lymph nodes detected by EUS in patients with esophageal carcinoma.

BACKGROUND: EUS determination of lymph nodal spread of intestinal cancer based on imaging alone is problematic. A noninvasive, reliable means of determining tumor spread to lymph nodes is desirable. This study investigated the feasibility of a computer-assisted evaluation of lymph nodes detected by EUS in patients with esophageal carcinoma. METHODS: Images were obtained during EUS of esophageal lesions and correlated with histopathologic findings after esophagectomy. Sonographic features of echogenicity, whole-node heterogeneity, and regional variability were assessed by computerized image analysis in patients with benign versus malignant lymphadenopathy. RESULTS: Malignant lymph nodes were hypoechoic compared with benign lymph nodes (p < 0.04). Whole lymph node heterogeneity was increased in malignant lymph nodes (p < 0.004). Regional variability was greater for benign lymph nodes. CONCLUSIONS: These data support the feasibility of a computer-assisted system for analysis of lymph node metastasis in patients with esophageal carcinoma. Further refinements of such a system could increase the accuracy of EUS staging of tumors.

Adenocarcinoma↗

The benefit of using two techniques for sentinel lymph node mapping in breast cancer.

Sentinel lymph node (SLN) mapping has revolutionized the way we stage breast cancer. A blue dye technique (BD) and the use of a radiotracer with the assistance of a gamma-detecting probe (GDP) have been used for the identification of the sentinel nodes. Some groups have suggested that only one technique is necessary. The reported false negative rates have been 0 to 12 per cent and success rates as low as 65 per cent. We have prospectively evaluated these techniques and have used both for the identification of the SLN. Ten surgeons participated in this study. From April 1998 through May 1999, 58 patients underwent SLN mapping followed by an axillary lymph node dissection. After the injection of 0.3 to 1.96 mCi of filtered sulfur colloid diluted to 4 mL all patients had preoperative lymphoscintigraphy. Five minutes before surgery 3 to 5 mL of isosulfan blue was injected around the tumor or tumor bed. Even though preoperative lymphoscintigraphy identified an SLN in 35 patients (63%) successful intraoperative detection of an SLN was possible using both techniques in 53 patients (91%). The SLN was detected by the BD and the GDP in 37 (65%) and 45 (80%) respectively. Nineteen patients (33%) were positive for metastatic disease in the axilla. Twenty-two (19%) of 113 SLNs removed were positive for disease. All cases of metastatic disease in the axilla were detected by the mapping technique. False negative rate was 0 per cent. In 11 patients the only positive node was the sentinel node (58%). Furthermore six (32%) patients were upstaged by the use of immunostains for cytokeratin. Twenty-two positive SLNs were detected in the 19 patients. The positive lymph node was identified only by BD in four patients (21%), only by GDP in six patients (31%), and by both techniques in nine patients (47%). We conclude that if only one technique had been used the false negative rate could have been as high as 32 per cent. Both techniques must be used to obtain a low false negative rate and high yield in the identification of the SLN.

Breast Neoplasms↗

An electron microscopic study on the reticuloendothelial cells in the lymph nodes.

In an attempt to clarify the cytological characteristics of the RES cells in the lymph nodes and their embryological correlations, lymph nodes and lymph node anlages of germ-free rats, nude mice, and human fetuses were light and electron microscopically examined. On the basis of differences of intracellular organelles, their behaviors for reticulum fibers and of endogeneous peroxidatic activity, histiocytes should be reasonably distinguished from the cells conventionally called reticulum cells. Reticulum cells and histiocytes respectively are destined to differentiate in different directions from the early stage of development of the lymph node anlage. Sinus endothelial cells are ontogenetically originated and differentiated from the endothelial lining cells of lymphatic vessels. Primitive reticular cells are differentiated into mature reticulum cells in the lymph nodes, they transform into the lympho-reticular cells, further into lymphoblasts, and finally develop into medium-sized lymphocytes.

Animals↗

Role of thyroglobulin measurement in fine-needle aspiration biopsies of cervical lymph nodes in patients with differentiated thyroid cancer.

The identification of metastatic neck lymph nodes in patients awaiting surgery for differentiated thyroid tumor permits their excision during thyroidectomy. In order to detect thyroid cancer lymphatic metastasis before surgery, we measured thyroglobulin (Tg) in the needle wash-out of fine-needle aspiration biopsy (FNAB). Ultrasound-guided FNAB on enlarged neck nodes was performed in 23 patients awaiting surgery for differentiated thyroid tumor (n = 33 lymph nodes), 47 patients previously thyroidectomized for thyroid tumor (n = 89 lymph nodes), and 60 patients without thyroid disease (n = 94 lymph nodes). Immediately after aspiration biopsy, the needle was rinsed with 1 mL of normal saline solution and Tg levels were measured on the needle wash-out (FNAB-Tg). FNAB-Tg levels were markedly elevated in metastatic lymph nodes both in patients awaiting thyroidectomy (metastatic vs. negative lymph nodes, mean +/- SEM, 16,593 +/- 7,050 ng/mL vs. 4.91 +/- 1.61 ng/mL; p < 0.001) and in thyroidectomized patients (11,541 +/- 7,283 ng/mL vs. 0.45 +/- 0.07 ng/mL; p < 0.001). FNAB-Tg sensitivity, evaluated through histological examination in 69 lymph nodes, was 84.0%. The combination of cytology plus FNAB-Tg increased FNAB sensitivity from 76% to 92.0%. In conclusion, FNAB-Tg measurement is a useful technique for early diagnosis of lymph node metastasis originating from differentiated thyroid cancer.

Adult↗

Intraoperative identification of esophageal sentinel lymph nodes with near-infrared fluorescence imaging.

OBJECTIVE: In esophageal cancer, selective removal of involved lymph nodes could improve survival and limit complications from extended lymphadenectomy. Mapping with vital blue dyes or technetium Tc-99m often fails to identify intrathoracic sentinel lymph nodes. Our purpose was to develop an intraoperative method for identifying sentinel lymph nodes of the esophagus with high-sensitivity near-infrared fluorescence imaging. METHODS: Six Yorkshire pigs underwent thoracotomy and received submucosal, esophageal injection of quantum dots, a novel near-infrared fluorescent lymph tracer designed for retention in sentinel lymph nodes. Six additional pigs underwent thoracotomy and received submucosal esophageal injection of CW800 conjugated to human serum albumin, another novel lymph tracer designed for uptake into distant lymph nodes. Finally, 6 pigs received submucosal injection of the fluorophore-conjugated albumin with an endoscopic needle through an esophagascope. These lymph tracers fluoresce in the near-infrared, permitting visualization of migration to sentinel lymph nodes with a custom intraoperative imaging system. RESULTS: Injection of the near-infrared fluorescent lymph tracers into the esophagus revealed communicating lymph nodes within 5 minutes of injection. In all 6 pigs that received quantum dot injection, only a single sentinel lymph node was identified. Among pigs that received fluorophore-conjugated albumin injection, in 5 of 12 a single sentinel lymph node was revealed, but in 7 of 12 two sentinel lymph nodes were identified. There was no dominant pattern in the appearance of the sentinel lymph nodes either cranial or caudal to the injection site. CONCLUSION: Near-infrared fluorescence imaging of sentinel lymph nodes is a novel and reliable intraoperative technique with the power to assist with identification and resection of esophageal sentinel lymph nodes.

Animals↗

Enlarged lymph nodes: malignant or not?

Prospective controlled data of lymph node evaluation by endoscopic ultrasound in esophageal, gastric and pancreatic cancer is presented. Lymph node pattern, changes of boundaries and echogenicity were considered. Preoperative findings of endoscopic ultrasound were classified according to TNM staging. Only those cases with subsequent histologic examination of the resected specimen were entered into the study. Sensitivity of endoscopic ultrasonography (EUS) was 90% for esophageal and 87% for gastric cancer. The specificity was 72% and 88%, respectively. In spite of the overall satisfactory results of EUS in evaluation of lymph nodes, further improvement in detection and differentiation of benign and malignant nodes is required.

Endoscopy, Digestive System↗

Metastatic lymph node ratio as a prognostic factor in gastric cancer.

BACKGROUND: There is an association between the number of resected lymph node and the number of metastatic lymph nodes in gastric cancer, suggesting that pN category could be influenced by the extension of the lymphadenectomy. This study evaluates this association and proposes a comprehensive use of the ratio as prognostic factor. METHOD: Review of 183 consecutive patients with gastric adenocarcinoma. The association between the number of resected lymph nodes and the number of metastatic lymph nodes was analysed and evaluated with other prognostic factors. RESULTS: The number of lymph node metastases increased with the number of resected lymph nodes. The lymph node ratio was a better prognostic factor than the number of metastatic lymph nodes. CONCLUSIONS: The metastatic lymph node ratio seems to be a good prognostic factor, but needs further evaluation.

Adenocarcinoma↗