Roger F. Uren

Prediction of potential metastatic sites in cutaneous head and neck melanoma using lymphoscintigraphy

BACKGROUND The technique of lymphoscintigraphy may allow a more selective approach to the management of clinically negative neck nodes among patients with cutaneous head and neck melanoma. PATIENTS AND METHODS A group of 97 patients with cutaneous head and neck melanoma had preoperative lymphoscintigraphy using intradermal injections of technetium 99m antimony trisulfide colloid to identify sentinel nodes. Fifty-one patients were eligible for clinical analysis after initial definitive treatment by wide excision only (n = 11), wide excision and elective dissection of the neck (n = 19) or axilla (n = 1), or wide excision and a sentinel node biopsy procedure (n = 20). RESULTS Sentinel nodes were identified in 95 of 97 lymphoscintigrams, and 85% of patients had multiple sentinel nodes. In 21 patients (22%), sentinel nodes were identified outside the parotid region and the 5 main neck levels, mostly in postauricular nodes (n = 13). Lymphoscintigrams were discordant with clinical predictions in 33 patients (34%). Lymph nodes were positive in 4 elective dissections and 4 sentinel node biopsies. Among 16 patients evaluable after wide excision and a negative sentinel node biopsy, 4 patients subsequently developed metastatic nodes; however, confident identification of all nodes marked as sentinel nodes on lymphoscintigraphy was not achieved at the original biopsy procedure in 3 of these patients. CONCLUSIONS Lymphoscintigraphy and sentinel node biopsy are more difficult to perform in the head and neck than in other parts of the body. The reliability of sentinel node biopsy based on lymphoscintigraphy may be improved by identifying and marking all nodes that are considered to receive direct lymphatic drainage from the primary melanoma, and by use of a gamma probe intraoperatively.

Location of sentinel lymph nodes in patients with cutaneous melanoma: new insights into lymphatic anatomy

BACKGROUND Accurate staging of melanoma patients by sentinel node (SN) biopsy can be achieved only if all SNs draining a given melanoma site are identified and removed for detailed histologic examination. Lymphoscintigraphy with a radiolabeled colloid provides an objective and reliable method of locating SNs and demonstrates that confident prediction of their location is not possible on clinical grounds. STUDY DESIGN Lymphatic drainage pathways demonstrated by preoperative lymphoscintigraphy for 1,759 patients with primary cutaneous melanomas were reviewed, and locations of SNs in these patients were documented. An SN was defined as any node receiving direct lymphatic drainage from a primary melanoma site. RESULTS In many instances the cutaneous lymphatic drainage pathways were found to be at variance with longheld concepts of lymphatic anatomy. Several new pathways were identified, draining to SNs in unexpected sites. These included triangular intermuscular space SNs (from upper back and, rarely, upper limb primaries), paraaortic and retroperitoneal SNs (from upper and lower back primaries), and costal margin SNs with onward drainage to internal mammary nodes (from periumbilical primaries). Occasional drainage to node fields on the opposite side of the body was noted from head, neck, and trunk primaries, and drainage to interval nodes (by definition, SNs) outside recognized lymph node fields was also observed. CONCLUSIONS Knowledge of the possibility of these unusual lymphatic drainage patterns and SN sites should help to ensure the accuracy and completeness of SN identification. Preoperative lymphoscintigraphy to definitively locate SNs is recommended for every patient undergoing an SN biopsy procedure.

Exercise-induced ST-segment elevation. Correlation of thallium-201 myocardial perfusion scanning and coronary arteriography.

Exercise-induced ST-segment elevation was correlated with myocardial perfusion abnormalities and coronary artery obstruction in 35 patients. Ten patients (group 1) developed exercise ST elevation in leads without Q waves on the resting ECG. The site of ST elevation corresponded to both a reversible perfusion defect and a severely obstructed coronary artery. Associated ST-segment depression in other leads occurred in seven patients, but only one had a second perfusion defect at the site of ST depression. In three of the 10 patients, abnormal left ventricular wall motion at the site of exercise-induced ST elevation was demonstrated by ventriculography. Twenty-five patients (group 2) developed exercise ST elevation in leads with Q waves on the resting ECG. The site of ST elevation corresponded to severe coronary artery stenosis and a thallium perfusion defect that persisted on the 4-hour scan (constant in 12 patients, decreased in 13). Associated ST depression in other leads occurred in 11 patients and eight (73%) had a second perfusion defect at the site of ST depression. In all 25 patients with previous transmural infarction, abnormal left ventricular wall motion at the site of the Q waves was shown by ventriculography.In patients without previous myocardial infarction, the site of exercise-induced ST-segment elevation indicates the site of severe transient myocardial ischemia, and associated ST depression is usually reciprocal. In patients with Q waves on the resting ECG, exercise ST elevation way be due to peri-infarctional ischemia, abnormal ventricular wall motion or both. Exercise ST-segment depression may be due to a second area of myocardial ischemia rather than being reciprocal to ST elevation.

Outcome in 846 Cutaneous Melanoma Patients From a Single Center After a Negative Sentinel Node Biopsy

BackgroundA negative sentinel node biopsy (SNB) implies a good prognosis for melanoma patients. The purpose of this study was to determine the long-term outcome for melanoma patients with a negative SNB.MethodsSurvival and prognostic factors were analyzed for 836 SNB-negative patients. All patients with a node field recurrence were reviewed, and sentinel node (SN) tissue was reexamined.ResultsThe median tumor thickness was 1.7 mm, and 23.8% were ulcerated. The median follow-up was 42.1 months. Melanoma specific survival at 5 years was 90%, compared with 56% for SN-positive patients (P < .001). On multivariate analysis, only thickness and ulceration retained significance for disease-free and disease-specific survival. Five-year survival for patients with nonulcerated lesions was 94% vs. 78% with ulceration. Eighty-three patients (9.9%) had a recurrence. Twenty-seven patients developed recurrence in the regional node field, and in 22 of these, it was the first recurrence site. Six developed local recurrence, 17 an in-transit metastasis, and 58 distant disease. The false-negative rate was 13.2%. SN slides and tissue blocks were further examined in 18 patients with recurrence in the node field, and metastatic disease was found in 3 of them.ConclusionsThis large, single-center study confirms that patients with a negative SNB have a significantly better prognosis than those with positive SNs. In those with a negative SNB, primary tumor thickness and ulceration are independent predictors of survival. Incorrect pathologic diagnosis contributed to only a minority of the false-negative results in this study.

EANM-EORTC general recommendations for sentinel node diagnostics in melanoma

The accurate diagnosis of a sentinel node in melanoma includes a sequence of procedures from different medical specialities (nuclear medicine, surgery, oncology, and pathology). The items covered are presented in 11 sections and a reference list: (1) definition of a sentinel node, (2) clinical indications, (3) radiopharmaceuticals and activity injected, (4) dosimetry, (5) injection technique, (6) image acquisition and interpretation, (7) report and display, (8) use of dye, (9) gamma probe detection, (10) surgical techniques in sentinel node biopsy, and (11) pathological evaluation of melanoma-draining sentinel lymph nodes. If specific recommendations given cannot be based on evidence from original, scientific studies, referral is given to “general consensus” and similar expressions. The recommendations are designed to assist in the practice of referral to, performance, interpretation and reporting of all steps of the sentinel node procedure in the hope of setting state-of-the-art standards for good-quality evaluation of possible spread to the lymphatic system in intermediate-to-high risk melanoma without clinical signs of dissemination.

Correlation between preoperative lymphoscintigraphy and metastatic nodal disease sites in 362 patients with cutaneous melanomas of the head and neck.

Objective:Lymphoscintigraphy for head and neck melanomas demonstrates a wide variation in lymphatic drainage pathways, and sentinel nodes (SNs) are reported in sites that are not clinically predicted (discordant). To assess the clinical relevance of these discordant node fields, the lymphoscintigrams of patients with head and neck melanomas were analyzed and correlated with the sites of metastatic nodal disease. Methods:In 362 patients with head and neck melanomas who underwent lymphoscintigraphy, the locations of the SNs were compared with the locations of the primary tumors. The SNs were removed and examined in 136 patients and an elective or therapeutic regional lymph node dissection was performed in 40 patients. Results:Lymphoscintigraphy identified a total of 918 SNs (mean 2.5 per patient). One or more SNs was located in a discordant site in 114 patients (31.5%). Lymph node metastases developed in 16 patients with nonoperated SNs, all underneath the tattoo spots on the skin used to mark the position of the SNs. In 14 patients SN biopsy revealed metastatic melanoma. After a negative SN biopsy procedure 11 patients developed regional lymph node metastases during follow-up. Elective and therapeutic neck dissections demonstrated 10 patients with nodal metastases, all located in predicted node fields. Of the 51 patients with involved lymph nodes, 7 had positive nodes in discordant sites (13.7%). Conclusions:Metastases from head and neck melanomas can occur in any SN demonstrated by lymphoscintigraphy. SNs in discordant as well as predicted node fields should be removed and examined to optimize the accuracy of staging.

Uremic Cardiomyopathy — Effect of Hemodialysis on Left Ventricular Function in End-Stage Renal Failure

Left ventricular ejection fraction was measured by radionuclide left ventriculography before and immediately after hemodialysis in 20 uremic patients, 11 of whom presented with congestive heart failure. Ejection fraction and contraction were normal in 15 patients (Group A), six of whom had signs of congestive failure; they were abnormal in five patients (Group B), all of whom were in clinical heart failure. Mean arterial pressure and body weight decreased by a similar amount after dialysis in both groups, and heart rate did not change. In Group A ejection fraction was unchanged by dialysis (0.63 +/- before vs. 0.62 +/- 0.09 after) (mean +/- S.D.), but in Group B it was improved significantly (0.32 +/- 0.04 before vs. 0.44 0.08 after) (P less than 0.01). In three patients in Group B cardiomegaly and ejection fraction returned to normal with long-term hemodialysis. In end-state renal failure, radionuclide left ventriculography can separate patients with circulatory congestion due to fluid overload from patients with left ventricular dysfunction in whom hemodialysis can provide immediate and long-term improvement.

Management of Merkel Cell Carcinoma: The Roles of Lymphoscintigraphy, Sentinel Lymph Node Biopsy and Adjuvant Radiotherapy

BackgroundMerkel cell carcinoma (MCC) is an uncommon, highly aggressive skin malignancy with a propensity to recur locally and regionally. However, its optimal treatment is uncertain. In this study, we aimed to assess the roles of lymphoscintigraphy and sentinel node (SN) biopsy, as well as radiotherapy, in the treatment of MCC.Patients and MethodsA retrospective analysis of 17 patients diagnosed with MCC (median age 74 years) over a 7-year period (median follow-up 16 months) was performed.ResultsOf 11 patients. 3 had a positive SN biopsy and, despite adjuvant radiotherapy, 2 of these 3 developed regional lymph node (RLN) recurrence. Of the remaining 8 patients who had a negative SN biopsy, however, 5 also had RLN recurrences. There were 9 patients who received adjuvant radiotherapy (RT) to the primary site, with no in-field recurrences; and 8 who received RT to their RLN field, with only 2 developing regional nodal recurrences—both were SN biopsy positive. During the follow-up period, 2 patients died, only 1 due to MCC.ConclusionThe results suggest that SN status may not be an accurate predictor of loco-regional recurrence in MCC. However, they strongly reinforce previous reports that radiotherapy, both locally and to regional nodes, provides effective infield disease control.

Comparison of thallium-201 scanning in idiopathic dilated cardiomyopathy and severe coronary artery disease.

To determine whether cardiomyopathy could be distinguished from coronary artery disease, we used thallium scanning to study 25 patients with severe left ventricular dysfunction and chronic heart failure. Ten patients had normal coronary arteries and idiopathic cardiomyopathy (ejection fraction 20 ± 5%), and 15 patients had multivessel coronary disease and left ventricular dysfunction (ejection fraction 25 ± 6%). The exercise time and maximal heart rate were similar in the two groups. Two patients with cardiomyopathy and 11 with coronary artery disease had a positive exercise ECG (p < 0.05). Thallium scans showed perfusion defects in all 25 patients. The perfusion defects were complete in nine coronary artery disease patients (60%) and in one patient (10%) with cardiomyopathy (p < 0.05). Extensive defects involving more than 40% of the left ventricular circumference, the number of segments involved, redistribution on the 4-hour scan, lung uptake and ventricular size were similar in the two groups. Perfusion defects on thallium scanning can occur in patients with idiopathic dilated cardiomyopathy and chronic heart failure. Thallium scanning cannot be reliably used in patients with chronic heart failure to distinguish coronary artery disease from cardiomyopathy unless complete defects are present.

Lymphatic mapping of the breast: locating the sentinel lymph nodes

When the concept of sentinel lymph node biopsy was described in patients with melanoma, researchers quickly started to use lymphatic mapping techniques in breast cancer patients in an attempt to locate the sentinel node in the axilla. We have been performing mammary lymphoscintigraphy in this role for 6 years and have now studied 159 patients. Like others, we have found that most breast cancers (93%) have lymphatic drainage that includes the axilla, and we have found an average of 1.4 axillary sentinel nodes in these patients. Surgical biopsy of the axillary sentinel nodes accurately staged the node field in 96% of patients. We have also found, however, that the pattern of lymphatic drainage from the cancer site is unpredictable; and in 49% of patients lymphatic drainage occurred across the center line of the breast to axillary or internal mammary sentinel nodes. In more than half of our patients (56%) lymphatic drainage occurred to lymph nodes outside the axilla including the internal mammary (45%), supraclavicular (13%), and interpectoral and intramammary interval nodes (12%). These nodes are also sentinel nodes, and their presence indicates that a sentinel node biopsy procedure that stages only the status of the axillary lymph nodes has the potential to understage about half the patients with breast cancer. High quality lymphoscintigraphy allows accurate mapping of peritumoral lymphatic drainage in most patients with breast cancer. It is possible that in the future accurate nodal staging in each individual will involve biopsy of all sentinel lymph nodes, regardless of their location.