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A prospective study of the value of axillary node sampling in addition to sentinel lymph node biopsy in patients with breast cancer.

AIMS: Limitations of sentinel lymph node biopsy (SLNB) include the occurrence of false negative (FN) results and the need to further treat SLNB positive axillae. The aims of this study were to: (1) compare the accuracy of SLNB alone to a combined SLNB and axillary sampling procedure (SLNB+AS). (2) evaluate if the additional AS could identify those SLNB positive cases with no further disease in the axilla. METHODS: Sixty-seven combined SLNB+AS procedures were performed prospectively in 66 patients, followed by Level II axillary dissection. Additionally sampled nodes were recorded if they were clinically suspicious or not at intra-operative palpation. RESULTS: The FN rate for SLNB alone was 14.3%, whilst that for SLNB+AS was reduced to 3.6%. However, the benefit of additional sampling was only seen in those cases with tumours >/=3 cm and clinically suspicious nodes (n=12). Of 12 cases with a positive SLN but negative AS, 4 (30%) were found to have disease elsewhere in the axilla. CONCLUSION: SLNB is inaccurate in the presence of suspicious nodes found at operation and careful palpation and sampling of these nodes is recommended, especially with larger tumours. In SLNB positive patients, AS is unreliable in predicting those patients with no further disease in the axilla.

Adult↗

[Color-coded duplex sonography in the differential diagnosis of cervical lymph node enlargements].

55 patients with cervical lymph node enlargement were studied prospectively by colour coded duplex sonography. The aim was to demonstrate the perfusion of individual lymph nodes and to determine whether the resistance and pulsatile index are able to show the cause of the enlargement. The lymph nodes were subsequently examined histologically. Useful perfusion measurements were obtained in 177 lymph nodes out of 216. Perfusion index < 1.6 and resistance index < 0.8 distinguishes between reactive lymph node enlargement and lymph node metastases with an accuracy of 91%. Reliable differentiation between lymphoma and metastases was not possible. Tuberculous lymph nodes and cysts showed significantly reduced resistance and pulsatile index when compared with metastases. Further information on the type of disease was obtained from the perfusion patterns. Reactive lymph nodes showed increased central perfusion of the hilum, whereas metastases tended to show increased peripheral perfusion.

Diagnosis, Differential↗

[Modified radical mastectomy and lymphocyte subsets of regional lymph nodes].

Whether or not regional lymph nodes in tumor-bearing hosts possess special immunological properties, still remains an important problem in the management of breast cancer. Regional lymph node cells from 22 patients with breast cancer were immunologically studied using monoclonal antibodies, OKT-3, 4, 8, OK-M 1, Leu-7, and laser flow cytometry. Among these patients, 13 early cancer patients underwent modified radical mastectomy (Auchincloss operation or Patey operation) and 9 underwent standard radical mastectomy (resection of breast, pectoralis major muscle and axillary dissection). More helper T lymphocytes defined by OKT-4 were found in regional lymph nodes in modified radical mastectomy patients in comparison with standard radical mastectomy patients. In patients given the modified operations, NK activity defined by OK-M 1 or Leu-7 were significantly increased, especially in lateral axillary lymph nodes. Also, OK-M 1 lymphocytes and Leu-7 lymphocytes were increased in lymph nodes without metastasis rather than those with metastasis. These findings suggest that regional lymph nodes may have defence mechanisms against the spread of tumor cells in early cancer patients.

Axilla↗

Anamnestic responses to contact allergens: application in the murine local lymph node assay.

The murine local lymph node assay, an alternative predictive test for the identification of contact sensitizing chemicals, is based upon the fact that skin allergens induce proliferation in lymph nodes draining the site of application. In the present study we have examined whether pre-exposure to the test chemical at a distant site enhances subsequent draining lymph node cell proliferation and, thereby, the sensitivity of the assay. Experiments were performed using both in vitro and in situ measurement of induced lymph node cell proliferation. It was found that, with the exception of potent skin sensitizers such as picryl chloride and oxazolone, which impair subsequent proliferative activity as a consequence of induced immunoregulatory processes, pre-treatment with the test allergen resulted in enhanced proliferation. Evidence is presented that the local lymph node assay response to a variety of skin allergens (including eugenol, isoeugenol, dihydrocoumarin, 4-vinylpyridine, cinnamic aldehyde and 2,4,5-trichlorophenol) was augmented when mice received a single exposure to the same chemical 5 days earlier. It is concluded that the use of a modified protocol, incorporating pre-exposure to the test material, can enhance local lymph node assay responses to all but the most potent skin allergens, and may be of particular value when increased sensitivity is required.

Allergens↗

Immunohistochemical demonstration of cytokeratin is useful for detecting micrometastatic foci from gallbladder carcinoma in regional lymph nodes.

BACKGROUND: The histological detection of lymph node metastasis in patients with gallbladder carcinoma is of major prognostic significance. However, it may be difficult to identify nodal involvement by conventional pathological examination of hematoxylin-eosin (HE)-stained sections when metastases are of microscopic size. In the present study, an attempt was made to detect lymph node metastasis precisely from gallbladder carcinoma, even by low-power microscopic examination, using immunohistochemistry with an anti-cytokeratin antibody. METHODS: A total of 431 lymph node specimens dissected during surgery from 33 patients with carcinoma of the gallbladder were investigated. A pair of mirror-image sections were obtained from each of the dissected lymph nodes and then stained using standard HE and immunohistochemical methods utilizing a monoclonal antibody against cytokeratin 7. The HE- and immunohistochemically stained sections were examined for the presence of tumor cells using light microscopy. RESULTS: All 78 lymph nodes from 12 patients with early gallbladder carcinoma were negative for both HE- and cytokeratin-positive cancer cells. Of 353 lymph nodes from 21 patients with advanced gallbladder carcinoma, HE staining showed that 98 were metastasis-positive. Among these 98 lymph nodes, 95 (97%) proved to be positive for metastasis based on cytokeratin immunostaining. On the other hand, the remaining 255 lymph nodes were cancer-free on the basis of HE staining results. Of the 255 HE-negative lymph nodes, seven (2.7%) were found to be positive for micrometastasis on the basis of cytokeratin staining. CONCLUSIONS: Cytokeratin staining of dissected lymph nodes is a useful new diagnostic tool for detecting micrometastatic foci in regional lymph nodes of patients with gallbladder carcinoma.

Adult↗

Clinical implications of contralateral axillary sentinel lymph nodes.

Extra-axillary sentinel lymph nodes can only be detected if radioactive tracer is used and pre-operative scans are carried out. The presence of metastatic sentinel lymph nodes in most extra-axillary sites will upstage patients if the ipsilateral axillary sentinel lymph node is normal. Paradoxically, the presence of metastatic sentinel lymph nodes in the contralateral axilla has the potential to prevent upstaging to stage IV, but only if detected as a sentinel node at the initial surgery rather than as a systemic recurrence at some later time. We describe a case of bilateral axillary sentinel lymph nodes detected by pre-operative lymphoscintigraphy in a patient with a medial quadrant breast cancer and discuss the possible implications of such a finding.

Axilla↗

The appearance of non-specific antibody-forming cells in the efferent lymph draining antigen-stimulated single lymph nodes.

Immunization of single lymph nodes with various antigens led to the appearance of cells in the efferent lymph that secreted antibody specific for the antigen which induced their formation and for a number of unrelated, non-crossreacting antigens. Immunization of single lymph nodes with mitogens led to the appearance of cells secreting antibodies specific for an even greater number of antigens, including one (TNP) that in all probability is not present in the animals' natural environment. When the node was primed with one antigen, a subsequent challenge with an unrelated antigen 12 weeks later led to the appearance of greater numbers of cells containing and secreting antibody against the previously experienced antigen, than was the case in unprimed lymph nodes. These findings indicate that the immune response to antigen provokes the maturation of lymphocytes of specificities unrelated to that of the injected immunogen. Such a mechanism may be important in maintaining immunological memory. Mitogens may directly activate lymphocytes into maturation and expression as antibody-secreting cells, whereas antigens appear to act indirectly.

Animals↗

Sentinel-node biopsy in axillary lymph-node staging for patients with multicentric breast cancer.

Multicentric breast cancer is thought to be a contraindication for sentinel-node biopsy by most clinicians. In a prospective study we took sentinel-node biopsy samples from 19 patients with multicentric invasive breast cancer with use of a blue dye and radiolabelled colloid mapping technique at the subareolar injection site. All patients underwent complete axillary dissection after sentinel-node biopsy. Nine patients had tumour-free and ten had metastatic sentinel nodes. The sentinel-node status was in concordance with the axillary sample in all patients. Sentinel-node biopsy might become an alternative to complete axillary dissection in patients with multicentric breast cancer with clinically negative lymph nodes.

Axilla↗

Wide-spread distribution of sentinel lymph nodes in esophageal cancer.

Sentinel lymph nodes are the first draining nodes that contain tumor cells. Identification of sentinel nodes may help to determine the suitable extent of lymphadenectoy. To assess the location of sentinel lymph nodes, a series of 41 patients with single and two metastatic lymph nodes who underwent esophagectomy and 3-field lymphadenectomy between 1991 and 1999 were investigated retrospectively. Only 29 (47.5%) of 61 metastatic nodes showed correspondence between the tumor site and the regional metastatic lymph nodes by routine histologic examination. In the patients with tumors in the upper and middle thoracic esophagus, metastatic lymph nodes were distributed in the cervix, mediastinum and abdomen. Although sentinel nodes were limited to the regional and adjusting compartments in 82%, nodes were found beyond the adjusting compartments in 18%. The sentinel nodes were broadly distributed depending on the location of the tumor in esophageal cancer.

Adult↗

Diagnosis and staging of lymph node metastasis.

The process of lymph node metastasis is not completely understood. Although we know some basic molecular mechanisms of metastasis, the exact procedure from the initiation of a primary tumour to overt lymph node metastasis remains obscure. A few morphological features of different primary tumours are known to correlate with the probability of lymph node metastasis, e.g., tumour histology (carcinoma vs. sarcoma), tumour size, T category, poor grade of differentiation and invasion of lymph vessels. Few attempts have been made to use markers of molecular differentiation such as nm23 as an additional indicator of lymph node metastasis. A drawback is the lack of an exact definition of lymph node metastasis or micrometastasis and how to include new findings such as the demonstration of cytokeratin-positive cells in "tumourfree" lymph nodes. Some of these aspects will be discussed within this review and proposals for classifications presented.

Classification↗

Validation of delayed sentinel lymph node mapping for melanoma.

PURPOSE: Sentinel lymph node mapping using radiolabeled tracer and blue dye is widely accepted and applied for staging melanoma. Common practice involves injection of radiolabeled tracer on the morning of surgery. However, optimal timing of radiolabeled colloid injection with respect to surgery remains debated. Injection on the day before surgery would offer the advantages of increased scheduling flexibility and decreased radiation exposure to the patient and operating room staff. We hypothesized that a single injection of radiolabeled colloid given 24 hours before surgery would be sufficient and would possibly improve intraoperative sentinel lymph node identification. PATIENTS AND METHODS: Ninety-five patients with newly diagnosed cutaneous melanoma underwent injection of radiolabeled colloid and lymphoscintigraphy 18 to 24 hours before surgery for sentinel lymph node mapping and biopsy. Sixty-three patients underwent repeat imaging immediately before surgery, and the images were compared with those obtained the previous day. Intraoperative mapping utilized a hand-held gamma probe and injection of blue dye to identify sentinel lymph nodes. RESULTS: Two hundred fifty-one sentinel lymph nodes were identified by initial lymphoscintigraphy in 95 patients. Delayed imagingwithout reinjection of radiolabeled tracer compared with the initial lymphoscintigraphy demonstrated no change (71%), clarification of initial ambiguous patterns (10%), or newly identified nodes (19%). Two hundred sixty-one sentinel lymph nodes were resected, of which 79% stained blue. Microscopic metastases were present in 20 sentinel lymph nodes (8%) in 19 patients (20%). All positive nodes contained radioactivity and blue dye. CONCLUSIONS: A single injection of radiocolloid 24 hours before surgery combined with intraoperative blue dye injection identified all sentinel lymph nodes and did not miss any metastatic disease. In addition, delayed imaging may clarify initial ambiguous findings and identify additional nodes at risk for metastasis. This technique produces sentinel lymph node identification rates, harvest rates, and rates of positivity comparable to those reported with the use of injection of radiolabeled tracer on the day of surgery and greatly facilitates the technical and administrative aspects of sentinel lymph node mapping.

Adolescent↗

Salmonella enterica in superficial cervical (prescapular) and ileocecal lymph nodes of slaughtered pigs.

Because certain lymph nodes may be incorporated in food products, the presence of Salmonella enterica in these tissues could pose a food safety risk. We designed this two-part study to assess the prevalence of Salmonella in prescapular lymph nodes from normal slaughtered swine. Prescapular lymph nodes were collected from 300 systematically selected pigs in study 1 and, in study 2, from 75 pigs distributed among 10 herds. For study 2, pooled bacterial cultures were also completed on ileocecal lymph nodes, combining tissue from five pigs per pool (n = 60 pools). No Salmonella was detected in study 1 among prescapular lymph nodes (95% confidence interval, 0.0 to 1.16%). Salmonella was not detected in 75 prescapular lymph nodes from study 2, although Salmonella was detected in 5 of 10 herds in ileocecal lymph nodes. We conclude that prescapular lymph nodes posed a limited food safety risk in this population of pigs.

Abattoirs↗

Impact of sentinel lymph node biopsy on the evolution of breast reconstruction.

BACKGROUND: Although sentinel lymph node biopsy is rapidly replacing complete axillary lymph node dissection for lymph node staging in women with clinically node-negative breast cancer, it is unclear what impact the transition to sentinel lymph node biopsy will have on the practice of breast reconstruction. METHODS: To determine the effect of the transition from complete axillary lymph node dissection to sentinel lymph node biopsy on their practice of breast reconstruction, the authors reviewed the records of 717 patients with breast cancer who underwent sentinel lymph node biopsy and 1887 breast reconstructions-487 were performed in patients who also underwent sentinel lymph node biopsy at The University of Texas M. D. Anderson Cancer Center between 1998 and 2003. RESULTS: Before 1999, sentinel lymph node biopsy was performed infrequently. Between 1999 and 2003, the number of sentinel lymph node biopsy procedures performed per year increased almost 50-fold. Concurrent with this increase in the use of sentinel lymph node biopsy, there was a corresponding increase in the proportion of breast reconstruction procedures performed in patients who had also undergone sentinel lymph node biopsy (13 percent per year, p = 0.0001). In 2003, 54 percent of all breast reconstructions were performed in patients who had sentinel lymph node biopsy. In 2000, 1 year after the use of sentinel lymph node biopsy began to increase, the choice of recipient vessels for free transverse rectus abdominis myocutaneous (TRAM) flap breast reconstruction began to change. Between 2001 and 2002, the internal mammary vessels replaced the thoracodorsal vessels as the preferred recipient vessels for TRAM flap reconstruction (p < 0.0001). Over the study period, the authors noted a decrease in the percentage of free TRAM flap procedures requiring revision, more frequent use of contralateral implant-based augmentation to achieve symmetry, an increase in the percentage of patients desiring a second attempt at reconstruction after loss of a TRAM flap, and a decrease in the percentage of patients being referred for physical therapy or treatment of lymphedema after free TRAM flap reconstruction. CONCLUSIONS: The transition from axillary lymph node dissection to sentinel lymph node biopsy has resulted in a change in breast reconstruction practices. The increased use of the internal mammary vessels reflects the decreased dissection of axillary tissue to expose the thoracodorsal vessels with sentinel lymph node biopsy in addition to concern that a subsequent axillary surgery to remove additional axillary nodes might injure the thoracodorsal vessels should they be used in breast reconstruction. Awareness of the decreased morbidity associated with sentinel lymph node biopsy has led patients to expect less morbidity and better aesthetic outcomes from TRAM flap reconstruction.

Axilla↗

Lymph node sampling in patients with epithelial ovarian carcinoma.

Lymph node sampling is part of the FIGO staging of patients with ovarian carcinoma and is usually part of a meticulous second look operation. We analyzed the primary lymph node status of patients and compared this to the lymph node status at second look operation. From 3/86-3/91, 97 patients with epithelial ovarian tumors were treated at this institution. Seventy-one of the 97 patients (73.2%) had lymph node sampling at primary surgery. Thirty of the 71 patients had positive lymph nodes (42.2%) and 41 patients were lymph node negative (57.8%). Of the initial 97 patients, 58 were eligible for second look operation (59.8%), and 48 of these patients had lymph nodes sampled at second look operation. Nine of the 48 patients had positive lymph nodes (18.7%) and 39 had negative lymph nodes at second look operation (81.3%). Of the patients with negative lymph nodes at primary surgery, 25 patients had second look operation and 24 of these patients had lymph node sampling at second look operation. All patients with negative lymph nodes at primary surgery had negative lymph nodes at second look operation. Of the 30 patients with positive lymph nodes at primary surgery, 12 underwent second look operation. Four patients had persistent positive lymph nodes and 8 patients had negative lymph nodes. Our data suggest that patients with negative lymph nodes at primary surgery are unlikely to have positive lymph nodes at second look operation. Therefore, we believe that lymph node sampling under these circumstances is unnecessary.

Adolescent↗

Immunocytological studies of lymph nodes in rheumatoid arthritis and malignant lymphoma.

Lymph nodes obtained from 9 patients with active rheumatoid arthritis were stained by immunological techniques permitting identification of B and T cell areas within the nodes. The lymph nodes were also compared with those obtained from patients with lymphoma. The rheumatoid lymph nodes showed prominent B cell staining in the follicular centres by the EAC and fluoresceinated immunoglobulin techniques. Interfollicular areas were intensely stained with anti-theta globulin. In contrast, lymphoma nodes stained less intensely with fluoresceinated immunoglobulins but stained like benign nodes with EAC. The difference in staining may reflect the degree of disorganisation of the neoplastic follicle and/or the different sensitivity of these 2 methods in the detection of B cells. The differences in staining are helpful in distinguishing the benign changes associated with chronic inflammation from neoplastic B cell proliferative changes seen in lymph nodes.

Arthritis, Rheumatoid↗