Is Lymphatic Mapping in Breast Cancer Adequate and Safe?

Lymphatic mapping with selective lymphadenectomy requires a concerted effort from the nuclear medicine physician, surgeon, and pathologist. Application of preoperative lymphoscintigraphy, and intraoperative use of both a gamma detection probe and a vital dye are recommended. This combined approach increases the likelihood of finding all sentinel nodes without removing nonsentinel nodes. A literature review of current experience reveals that the sentinel node can be found in more than 90% of the patients. When confirmatory lymphadenectomy follows, the false-negative rate can be kept down to about 5% after a certain learning phase. The sensitivity of this novel approach to detect lymphatic dissemination is currently overestimated because lymph node metastases in patients with a tumor-free sentinel node are probably overlooked. This shortcoming will be compensated by the more accurate pathologic evaluation of a sentinel node and the finding of sentinel nodes outside the axilla. Therefore the procedure is probably adequate and safe in patients at low risk of having disseminated disease. Lymphatic mapping with sentinel node biopsy is rapidly becoming the standard of care.     

The posterior lymphatic network of the breast rediscovered

Although the posterior lymphatic network of the breast has been described at the end of the 18th century, this anatomical entity had been almost forgotten. The observation of an increased visualization of extra-axillary sentinel nodes after image guided intralesional radiocolloid injection in non-palpable breast tumors has focused our attention again on the lymphatics on the posterior surface of the breast.     

Palliative isolated limb perfusion for advanced limb disease in stage IV melanoma patients

INTRODUCTION: Two to three percent of the patients with extremity melanoma develop in-transit metastases in the course of their disease. When local treatments fail, isolated limb perfusion (ILP) is a reasonable option, but is generally only applied to patients without evidence of distant metastases. We assessed the value of ILP in stage IV melanoma patients with symptomatic unresectable limb melanoma at our institutions. PATIENTS AND METHODS: A computerized database, containing all patient, tumor, ILP, and follow-up data of 505 ILPs performed in 451 patients between 1978 and 2001, allowed the selection of eight (1.8%) stage IV patients who underwent a palliative ILP for unresectable melanoma lesions on the limbs. All patients had high tumor burden limb disease, according to the combined Fraker and Rossi criteria. RESULTS: The overall tumor response rate was 88%, with 13% complete and 75% partial response rates. One patient did not respond to ILP. Three partial responding patients attained a complete remission (CR) after excision of the remaining limb lesions. The median duration of hospital stay was 12 days and acute regional toxicity was mild with slight erythema and edema in six and no signs of reaction in two patients. The median limb recurrence-free interval after CR was 6 months and the median duration from the time of distant metastases to death was 15 months. Overall ILP leads to the desired palliative effect in six patients (75%). CONCLUSION: ILP should be considered as a palliative treatment in selected stage IV melanoma patients with symptomatic advanced limb disease.     

Normal values of serum S-100B predict prolonged survival for stage IV melanoma patients

The value of normal S-100B levels to predict survival was evaluated in 145 patients with stage IV melanoma. Treatment consisted of temozolomide given alone or was followed by combined cytokine immunotherapy, given every three to four weeks, with an evaluation of response following two treatment-cycles. S-100B values were measured prior to and following each cycle of systemic therapy and regularly thereafter. Patients with normal initial S-100B values (n=32) had higher response rates and fewer and more favourable metastatic sites with better overall survival rates than patients with elevated S-100B levels (median 14.0 versus 6.6 months). Normal S-100B values increased in nearly all patients (28/31) after a median of 7.9 months. In addition, patients with rapid normalisation of their serum level (n=12) following systemic treatment experienced prolonged survival. However, upon multivariable analysis S-100B prior to treatment lost its independence as a prognostic factor, whereas lactate dehydrogenase (LDH) remained. When measured after treatment, both markers had independent value.     

Frozen Section Investigation of the Sentinel Node in Malignant Melanoma and Breast Cancer

Background: Intraoperative frozen section investigation allows immediate regional lymph node dissection when the sentinel node contains tumor. The purpose of this study was to determine the sensitivity of frozen section diagnosis of the sentinel node in melanoma and breast cancer patients.Methods: A total of 177 sentinel nodes from 99 melanoma patients and 444 lymph nodes from 262 breast cancer patients were assessed by frozen section investigation. Nodes were bisected, and a complete cross-section was obtained for frozen section. Step sections at three levels were made of the remaining lymphatic tissue and were stained with hematoxylin and eosin and S100/HMB45 (melanoma) or CAM5.2 (breast cancer) to obtain a final pathological diagnosis.Results: Frozen section investigation revealed metastases in 8 of 17 node-positive melanoma patients (47%). Seventy-one of 96 breast cancer patients (74%) with lymph node metastases were identified with frozen section. The specificity was 100% and 99%, respectively.Conclusion: The sensitivity of intraoperative frozen section investigation of sentinel nodes was 47% in melanoma patients and 74% in breast cancer patients. Frozen section examination allows immediate axillary lymph node dissection in the majority of node-positive breast cancer patients. Frozen section analysis is not recommended in patients with melanoma.Presented, in part, at the 4th World Conference on Melanoma, Sydney, Australia, June 10–14, 1997, and the 10th Congress of the European Society of Surgical Oncology, Groningen, the Netherlands, April 5–8, 2010434_2001_Article_222.     

The Value of Cloquet’s Node in Predicting Melanoma Nodal Metastases in the Pelvic Lymph Node Basin

Background: A selection of melanoma patients with groin metastases can benefit from a pelvic (iliac/obturator) lymph node dissection in addition to the infrainguinal dissection. However, there are no reliable criteria to determine which patients may benefit from such an inguinal-pelvic lymphadenectomy.Methods: In 142 patients (group A) out of a review of 214 groin dissections performed between 1980 and 1994, the tumor status of Cloquets node was traced retrospectively. In 52 additional patients (group B), the status of Cloquets node was registered prospectively. The number of positive lymph nodes and the total numbers of retrieved nodes were recorded as well. All patients underwent a combined therapeutic inguinal-pelvic lymph node dissection between January 1995 and June 1999 in a tertiary referral center.Results: Cloquets node was free of disease in 18 of 39 patients with involved pelvic nodes in the retrospective study (sensitivity, 54%; negative predictive value, 83%). In the prospective study, 9 of the 20 patients with involved pelvic nodes had a tumor-free Cloquets node (sensitivity, 55%; negative predictive value, 78%). Additional immunohistochemical staining of Cloquets node resulted in a sensitivity of 65%. In the combined group A&B, the number of positive nodes in the inguinal region (cutoff point more than three nodes) had a sensitivity of 41% and a negative predictive value of 78% to determine the pelvic nodal status. When we combined the number of positive inguinal nodes and Cloquets node in group A&B, the best sensitivity was 56% and the best negative predictive value was 82%.Conclusions: Cloquets node has a low sensitivity to predict the pelvic nodal tumor status. This was barely improved when we accounted for the number of positive inguinal nodes. Groin lymph node dissections should encompass the iliac and obturator compartments in patients with palpable inguinal node metastases.     

Anatomy and physiology of lymphatic drainage of the breast from the perspective of sentinel node biopsy

Knowledge of the anatomy and physiology of the lymphatic system is helpful when considering a particular sentinel node biopsy technique. The delicate balance between internal and external pressures in a lymphatic channel can be influenced by the injection volume and by massage in a negative or positive way. The narrow openings in the interendothelial junctions determine the speed of clearance of particles with a certain size, and this has implications for the timing of lymphoscintigraphy and surgery. Tracer uptake and lymph flow are highly variable and depend on a number of factors, some of which are beyond our control. The lymphatic anatomy is not completely understood despite numerous studies since the end of the 18th century. Several topics have been elucidated in more recent studies and through experience with sentinel node biopsy. First, although axillary drainage is the principal lymphatic path of the breast, any drainage pattern from any quadrant of the breast can occur. Second, most lymph from the breast flows to the nodal basins with a direct course, not passing through the subareolar plexus. Another relevant point is that gentle massage encourages lymph flow and facilitates sentinel node detection. What problems do we still face in clinical practice? The optimum size and number of labeled colloid particles remain to be established. The optimum volume of the tracer also remains to be determined. But the main controversy concerns the injection site. Although the intradermal injection technique has attractive practical features, there is currently insufficient certainty that drainage of tracer injected anywhere in or underneath the skin of the breast reflects drainage from the cancer. Connections between collecting lymphatic vessels from the tumor site and the collecting vessels from the skin and subdermal lymphatics can explain the concordance between intraparenchymal and superficial injections in most patients. To determine the technique that yields the best sentinel node identification rate with the lowest possible false-negative rate would require a large randomized trial with all patients undergoing a complete lymph node dissection and evaluation of all other axillary lymph nodes with serial sections and immunohistochemistry. Current knowledge about sensitivity is based on examination of the other axillary nodes with hematoxylin and eosin staining and not with immunohistochemistry, with the exception of two studies. (33,76) In addition, a complete level I to III dissection may not have been done in all patients, and it is not certain that pathologists removed and examined all the nodes from the specimens. The proposed study seems impossible now that routine axillary node dissection has been abandoned by the larger centers around the world. Choosing the most attractive approach requires determining the aim of lymphatic mapping. A superficial injection technique may be adequate when the purpose is to spare patients without lymph node metastases in the axilla an unnecessary axillary node dissection. An intraparenchymal injection technique should be used when the additional purpose is to determine the stage as accurately as possible and to identify sentinel nodes elsewhere.