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Biomedical subjects

B B Kroon

Publications and source records attributed to B B Kroon.

At least 19 recordsLinked to original sources

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.

Breast Neoplasms↗

History of sentinel node and validation of the technique.

Sentinel node biopsy is a minimally invasive technique to select patients with occult lymph node metastases who may benefit from further regional or systemic therapy. The sentinel node is the first lymph node reached by metastasising cells from a primary tumour. Attempts to remove this node with a procedure based on standard anatomical patterns did not become popular. The development of the dynamic technique of intraoperative lymphatic mapping in the 1990s resulted in general acceptance of the sentinel node concept. This hypothesis of sequential tumour dissemination seems to be valid according to numerous studies of sentinel node biopsy with confirmatory regional lymph node dissection. This report describes the history and the validation of the technique, with particular reference to breast cancer.

Biopsy↗

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 Cloquet's node was traced retrospectively. In 52 additional patients (group B), the status of Cloquet's 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: Cloquet's 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 Cloquet's node (sensitivity, 55%; negative predictive value, 78%). Additional immunohistochemical staining of Cloquet's 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 Cloquet's node in group A&B, the best sensitivity was 56% and the best negative predictive value was 82%. CONCLUSIONS: Cloquet's 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.

Adolescent↗

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.

Breast Neoplasms↗

Single intralesional tracer dose for radio-guided excision of clinically occult breast cancer and sentinel node.

BACKGROUND: The purpose of this study was to determine the feasibility of both lymphatic mapping and probe-guided primary tumor excision by use of intralesional tracer administration in clinically occult breast cancer. METHODS: Sixty patients with a clinically occult breast lesion were prospectively included. Lymphoscintigraphy was performed after intratumoral injection of 99mTc-labeled nanocolloid guided by ultrasound or stereotaxis. A catheter over a localization wire was inserted for intraoperative blue dye administration by using the same imaging techniques. After sentinel node identification, the gamma-ray detection probe was used for radio-guided wide local excision in patients who underwent breast-conserving therapy. RESULTS: A sentinel node was visualized on the scintigrams in 56 patients (93%) and could be identified intraoperatively in 58 patients (97%). A sentinel node contained tumor in 10 (17%) of these patients. Extra-axillary sentinel nodes were visualized in 43%, were collected in 38%, and contained metastasis in 7% of the patients. Complete excision of the primary tumor could be accomplished in 39 (87%) of 45 patients. CONCLUSIONS: Both sentinel node biopsy and probe-guided excision of a nonpalpable breast cancer is feasible with the aid of intralesional tracer administration. Sentinel node metastasis was found in 17% of the patients. A remarkably high percentage of extra-axillary drainage (43%) was observed.

Adenocarcinoma↗

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.

Breast↗

Sentinel nodes outside lymph node basins in patients with melanoma.

BACKGROUND: Lymphoscintigraphy occasionally reveals hot spots outside lymph node basins in patients with melanoma. The aim of this study was to evaluate such abnormally located hot spots. METHODS: Sentinel node biopsy was studied prospectively in 379 patients with clinically localized cutaneous melanoma. One day after lymphoscintigraphy, sentinel node biopsy was performed guided by vital blue dye and a gamma ray detection probe. RESULTS: Persisting hot spots outside the regional node basins were seen in 25 patients (6.6 per cent). Several specific drainage patterns were discerned. In five patients, aberrant sentinel nodes were not explored. The hot spot represented a lymphangioma in two patients. Radioactive lymph nodes were identified in the remaining 18 patients (4.7 per cent). Four patients had metastasis in one of these aberrant lymph nodes. CONCLUSION: Sentinel nodes were found outside a lymph node basin in 5 per cent of patients. Particular drainage patterns exist. It is recommended to incorporate such sites in the late scintigraphy images and to pursue aberrant sentinel nodes, as they may be the only sites of metastasis.

Biopsy↗

Regional toxicity after isolated limb perfusion with melphalan and tumour necrosis factor- alpha versus toxicity after melphalan alone.

AIMS: To determine whether the addition of high-dose tumour necrosis factor-alpha (TNF alpha) to isolated limb perfusion (ILP) with melphalan increases acute regional tissue toxicity compared to ILP with melphalan alone. METHODS: A retrospective, multivariate analysis of toxicity after normothermic (37--38 degrees C) and 'mild' hyperthermic (38--40 degrees C) ILPs for melanoma was undertaken. Normothermic ILP with melphalan was performed in 294 patients (70.8%), 'mild' hyperthermic ILP with melphalan in 71 patients (17.1%) and 'mild' hyperthermic ILP with melphalan combined with TNF alpha in 50 patients (12.0%). Toxicity was nil or mild (grades I--II according to Wieberdink et al.) in 339 patients (81.7%), and more severe acute regional toxicity (grades III--V) developed in 76 patients (18.3%). A stepwise logistic regression procedure was performed for the multivariate analysis of prognostic factors for more severe toxicity. RESULTS: On univariate analysis, 'mild' hyperthermic ILP with melphalan plus TNF alpha significantly increased the incidence of more severe acute regional toxicity compared to normothermic and 'mild' hyperthermic ILP with melphalan alone (36% vs 16% and 17%; P=0.0038). However, after ILP using TNF alpha no grade IV (compartment compression syndrome) or grade V (toxicity necessitating amputation) reactions were seen. Significantly more severe toxicity was seen after ILPs performed between 1991 and 1994 compared with earlier ILPs (33%vs 14%P=0.0001). Also, women had a higher risk of more severe toxicity than men (22% vs 7%; P=0.0007). After multivariate analysis, prognostic factors which remained significant were: sex (P=0.0013) and either ILP schedule (P=0.013) or treatment period (P=0.0003). CONCLUSIONS: Regional toxicity after 'mild' hyperthermic ILP with melphalan and TNF alpha was significantly increased compared to ILP with melphalan alone. This may be caused by increased thermal enhancement of melphalan due to the higher tissue temperatures (39--40 degrees C) at which the melphalan in the TNF alpha-ILPs was administered or by an interaction between high-dose TNF alpha and melphalan.

Adult↗

Improved sentinel node visualization in breast cancer by optimizing the colloid particle concentration and tracer dosage.

Faint lymph uptake may hamper sentinel node (SN) identification by scintigraphy and subsequent gamma probe localization. The aim of the present study was to evaluate an adjustment in the colloid particle concentration and tracer dosage to optimize mammary lymphoscintigraphy. Scintigraphy was performed in 151 patients with a palpable breast carcinoma and clinically negative axilla: for the first 75 patients (group A) a standard labelling of 0.5 mg nanocolloid with 99Tcm was performed, for the subsequent 76 patients (group B) the labelling dilution volume was reduced from 4 to 2 ml. For both groups the volume of injection was 0.2 ml. Lymph node uptake was evaluated by a 4-step visual score (from 0 = absent to 3+ = very intense), and by count quantification of at 4 h in the first draining SN. The SN visualization rate increased from 93% (70/75) in group A (mean dosage 93.4 MBq, range 57-130 MBq) to 99% (75/76) in group B (mean dosage 106.5 MBq, range 74-139 MBq). The percentage of patients with uptake 3+ was significantly higher (P = 0.001) in group B (51% vs 35% in group A). SN counts were significantly higher for group B (P<0.001). The percentage of patients with less than 2000 counts/node diminished from 45% in group A to 9% in group B (P = 0.001). In group B (P = 0.033) more lymph channels (53% vs 35% in group A) were visualized and for a longer time (26% vs 4% at 4 h). Axillary drainage was seen in 96% in group A and 98% in group B whereas non-axillary drainage was observed in 19% and 25%, respectively. Intraoperative SN identification rate was 97% in group A and 100% in group B. SN metastases were found in 41% of group A and 47% of group B. It is concluded that enhancement of colloid particle concentration and adjustment of tracer dosage led to improved SN identification by substantial increase in lymph node uptake and lymph vessel depiction. A significant reduction of cases with faint SN uptake enables better surgical efficacy.

Adult↗

The European Society of Surgical Oncology.

Surgery is the key to local tumor control and survival in the vast majority of cancer patients. Optimally performed oncological operations, based both on a profound knowledge of the disease and on organ-based technical expertise are therefore essential. In this field the multinational European Society of Surgical Oncology (ESSO) wants to play a pivotal role, improving surgical treatment and encouraging and promoting education and training in surgical oncology at all levels. To achieve this goal the ESSO is of the opinion that recognition of surgical oncology as a separate subspecialty has to pursued.

Accreditation↗

Isolated limb perfusion: the European experience.

Isolated limb perfusion (ILP) is a method of cancer treatment allowing the administration of high doses of anticancer agents in a limb surgically isolated from systemic circulation. By using continuous leakage monitoring and using the drug melphalan, a high complete remission rate is obtained in patients with melanoma. In patients with sarcomas, ILP with tumor necrosis factor and melphalan represents a neoadjuvant treatment for limb-sparing surgery. This treatment is the first demonstration of an active anti-angiogenic regimen in the clinic.

Antineoplastic Agents↗

Lymphatic mapping with intralesional tracer administration in breast carcinoma patients.

BACKGROUND: The objectives of the study were to determine how often a sentinel lymph node is visualized by lymphoscintigraphy in breast carcinoma patients, how often the sentinel lymph node is identified during surgery, and the sensitivity of these procedures to identify the presence of axillary lymph node metastasis. METHODS: A total of 136 patients were enrolled in 2 hospitals. Preoperative dynamic and static lymphoscintigraphy were performed; in addition, both a vital dye and a gamma detection probe were used intraoperatively. The tracers were injected into the primary lesion. Sentinel lymph node biopsy was followed by completion axillary lymph node dissection. The sentinel lymph nodes and other axillary lymph nodes were examined routinely and by immunohistochemical staining. RESULTS: A sentinel lymph node was visualized by lymphoscintigraphy in 118 patients (87%). During the operation a sentinel lymph node was localized in 126 patients (93%). A total of 224 sentinel lymph nodes were harvested (average of 1.7 and range of 1-4 sentinel lymph nodes per patient). Of all the sentinel lymph nodes, 37 were blue (17%), 68 were radioactive (30%), and 119 were both blue and radioactive (53%). The sentinel lymph nodes contained metastatic disease in 56 patients (44%). Three sentinel lymph node biopsies were false-negative (sensitivity 95%). CONCLUSIONS: Sentinel lymph node biopsy with preoperative lymphoscintigraphy after intralesional tracer administration and intraoperative use of both a gamma detection probe and a vital dye is a reliable technique for staging the axilla of breast carcinoma patients.

Adult↗

Sentinel node biopsy for melanoma in the head and neck region.

BACKGROUND: Lymphatic drainage in the head and neck region is known to be particularly complex. This study explores the value of sentinel node biopsy for melanoma in the head and neck region. METHODS: Thirty consecutive patients with clinically localized cutaneous melanoma in the head and neck region were included. Sentinel node biopsy was performed with blue dye and a gamma probe after preoperative lymphoscintigraphy. Average follow-up was 23 months (range, 1-48). RESULTS: In 27 of 30 patients, a sentinel node was identified (90%). Only 53% of sentinel nodes were both blue and radioactive. A sentinel node was tumor-positive in 8 patients. The sentinel node was false-negative in two cases. Sensitivity of the procedure was 80% (8 of 10). CONCLUSIONS: Sentinel node biopsy in the head and neck region is a technically demanding procedure. Although it may help determine whether a neck dissection is necessary in certain patients, further investigation is required before this technique can be recommended for the standard management of cutaneous head and neck melanoma.

Adult↗

Reliability of lymphoscintigraphy in indicating the number of sentinel nodes in melanoma patients.

BACKGROUND: This study was undertaken to establish the reliability of lymphoscintigraphy in indicating the number of sentinel nodes in patients with melanoma. METHODS: Lymphoscintigraphy was performed with dynamic imaging after injection of 60 MBq 99mTc-nanocolloid (1.6 mCi) and static imaging after 2 hours in 200 patients with clinically localized primary melanoma of the skin. The following day, sentinel nodes were retrieved with the blue dye technique and a gamma detection probe (Neoprobe 1000/1500). The discrepancies between the number of sentinel nodes indicated by lymphoscintigraphy and the actual number of sentinel nodes as established by the surgeon were evaluated. RESULTS: Lymphoscintigraphy showed drainage to 393 sentinel nodes in 255 lymphatic fields in 199 patients. In 48 lymphatic fields (19%) in 46 patients (23%), the number of sentinel nodes was different from the number that was visualized with scintigraphy. Additional sentinel nodes were found by the surgeon because a lymphatic vessel was not seen on the lymphoscintigraphy (43%), because a sentinel node was not visualized separately from other hot nodes or vessels or the injection site (36%), or because a sentinel node was blue and not hot (4%). Fewer sentinel nodes were found than suggested by scintigraphy because a lymphangioma was mistaken for a sentinel node (4%) or because a single elongated node was depicted as two hot spots (6%). CONCLUSIONS: Although lymphoscintigraphy is indispensable for lymphatic mapping, the predicted number of sentinel nodes is accurate in only 81% of lymph node fields. The limited discriminating power of the gamma camera is an important cause of discrepancies.

Adolescent↗