Harry Vogt

The Sentinel Lymph Node Concept in Prostate Cancer – First Results of Gamma Probe-Guided Sentinel Lymph Node Identification

Objective: The goal of this study was to show lymphatic drainage and to verify the validity of lymphoscintigraphy for the identification of the sentinel lymph node (SLN) in prostate cancer. Furthermore, the question is to be raised whether the standardized pelvic lymphadenectomy is a sufficient means for also detecting solitary micrometastases. Patients and Methods: Eleven patients with prostate cancer received a sonographically controlled, transrectal administration of a technetium-99m colloid injected directly into the prostate 1 day prior to pelvic lymphadenectomy. 20 min later the dynamic lymphoscintigraphy was carried out. During surgery, the SLNs were identified by using a gamma probe. The standard pelvic lymphadenectomy was performed after removal of the SLN. Results: In 3 of 4 patients with micrometastasis the spread of the tumor could exclusively be found in those nodes which had been identified as SLNs by means of scintigraphy by combining preoperative lymphoscintigraphy and intraoperative gamma probe detection. In 2 cases, the pathologically proved SLNs were situated at the anteromedial region of the internal iliac artery, thus being located outside of the standard pelvic lymphadenectomy area. In 1 patient, however, the micrometastasis was found beyond those nodes which had been identified as SLN intraoperatively. Conclusions: In the future, we expect the restriction of pelvic staging lymphadenectomy to scintigraphically proved SLN. The perioperative morbidity may be reduced by increasing the sensitivity of the detection of micrometastases. Our data confirm earlier perceptions, according to which even modified standardized pelvic lymphadenectomy is considered insufficient in terms of the detection of micrometastases.

RADIOISOTOPE GUIDED PELVIC LYMPH NODE DISSECTION FOR PROSTATE CANCER

PURPOSE The localization of lymph node metastases in prostate cancer varies enormously. Due to high morbidity complete pelvic lymphadenectomy is often decreased to modified staging lymphadenectomy, resulting in loss of sensitivity for detecting micrometastases. Based on the promising results of intraoperative gamma probe application for identifying sentinel lymph nodes in malignant melanoma, breast and penis cancer, we identified sentinel lymph nodes in prostate cancer using a comparable technique. MATERIALS AND METHODS In 117 patients 99mtechnetium nanocolloid was transrectally injected directly into the prostate under ultrasound guidance 1 day before pelvic lymphadenectomy. Thereafter dynamic lymphoscintigraphy was done. Initially lymph nodes identified as sentinel lymph nodes by the gamma probe were removed and subsequently modified pelvic lymphadenectomy was performed. RESULTS Lymphatic metastasis was detected in 28 cases. An average of 4 sentinel lymph nodes were identified per patient in 25 of 27 patients with micrometastasis, of which those in 24 contained micrometastasis for 96% sensitivity. In contrast, sensitivity of modified pelvic lymphadenectomy was 81.5%. In 16 patients only sentinel lymph nodes were positive. An average of 21.8 lymph nodes (range 10 to 51) was dissected per patient at pelvic lymphadenectomy. Lymph node metastasis was noted in 6 of the 46 patients with a prostate specific antigen between 4 and 10 ng./ml. and in 8 of the 64 with a stage pT2 tumor. CONCLUSIONS Our study shows individual variability of lymphatic drainage of the prostate and limited sensitivity for detecting positive lymph nodes when the pelvic dissection area is limited. Furthermore, our experience implies that the identification of sentinel lymph nodes is feasible, not only in breast cancer and malignant melanoma, but also in prostate cancer using a comparable technique.

The Influence of Serial Sections, Immunohistochemistry, and Extension of Pelvic Lymph Node Dissection on the Lymph Node Status in Clinically Localized Prostate Cancer

OBJECTIVES Pelvic lymph node metastases indicate a poor prognosis for patients with clinically localized prostate cancer. The aim of the study was to investigate the value of extended histopathological techniques considering the extent of pelvic lymphadenectomy and preoperative risk factors. METHODS Total of 194 patients with prostate cancer were examined. At first all patients had a sampling of the sentinel lymph nodes (SLN) followed in most cases by a modified or extended pelvic lymphadenectomy. Step sections, serial sections and immunohistochemistry (IHC, pancytokeratin antibody) were analyzed in all SLN and so-called non-SLN of the first 100 patients. Later serial sections and IHC of non-SLN were left out. RESULTS In 26.8% lymphatic metastases were found. The detection rate of lymph node-positive patients depend significantly on the chosen extension of pelvic lymphadenectomy. Limiting the histopathological investigation to the lymph node specimen of the obturator fossa only 44.2% of lymph node-positive cases would have been identified. An additional inclusion of all lymph nodes surrounding the external iliac vessels improves the sensitivity to 65.4% (46.7% and 73.3% for the first 100 patients). Compared to the extension of pelvic lymphadenectomy the diagnostic gain of serial section and IHC (13.8% versus 53.3%) was comparably low. CONCLUSIONS The extension of pelvic lymph node dissection is of outstanding value for the identification of node-positive patients. Limiting the number of lymph nodes to the ones with the highest probability of bearing lymphatic spread (SLN) makes the use of extensive histopathological techniques more feasible.

First experience with gamma probe guided sentinel lymph node surgery in penile cancer

Abstract Because of the curative approach, the detection of lymph node metastases in squamous cell carcinoma (SCC) of the penis is of significant clinical relevance. Sentinel lymph node (SLN) identification by means of lymphangiography has been proven to be insufficiently safe. However, the high morbidity of inguinal lymphadenectomy and the considerable individual variability regarding the location of lymph node metastases justify the necessity of a technique that enables the identification of SLNs. Since 1998, SLNs have been intraoperatively identified and selectively dissected, after peritumoral injection of technetium-99m nanocolloid and using lymphoscintigraphy, in three patients (one with malignant melanoma and two with SCC). At least one SLN could be detected in each patient. The maximum surgical time was 30 min. There were no severe complications. Lymph node metastases did not occur in any patient. Upon a mean follow-up of 10 months, all patients are currently free of tumor. Owing to the long-term results of sentinel lymphadenectomy in malignant melanoma of other locations and our preliminary results with respect to penile carcinoma, we consider the current method appropriate as the only primary operation for lymph node staging in early stages and, in combination with modified inguinal lymphadenectomy, in locally advanced stages.

Primary therapy of malignant melanomas: sentinel lymphadenectomy.

Background Each melanoma is drained by one or, occasionally, several individual lymph nodes within the nearest lymph node region (sentinel lymph node).

Lymph node staging in clinically localized prostate cancer.

Lymph node metastases are relatively often revealed in supposedly localized prostate cancers at the time of surgery. Data as for the frequency of this manifestation largely differ depending on the treat ed population and the extent and technique of pelvic staging lymphadenectomy. While large US studies revealed lymph node-positive stages in only 12%, we detected lymph node metastases in nearly 30% in own investigations. None of the currently avail able means of radiologic imaging provides sufficient diagnostic safety. The use of predictive nomograms for the forecast of the lymph node status does not offer a sufficient grade of reliability to the majority of patients. Thus, surgical lymph node staging remains indispensable. Although nomograms are partly based on results from studies with large patient populations, the performance of distinctively limited forms of pelvic lymphadenectomy remains an uncertainty. As a rule of thumb one can state that up to 50% of lymph node-positive patients are not recognized as such, if approximately 10 pelvic lymph nodes are dissected. When removing 20 pelvic lymph nodes about 25% of lymph node-positive patients are missed. An extensive or - in case of sufficient experience - gamma probe-guided pelvic lymphadenectomy has to be postulated for an exact definition of risk groups regarding lymphatic spread and for the validation and development of radiologic imaging. By combining preoperative lymphoscintigraphy and intraoperative gamma probe detection we have developed a method which enables us to identify the primary lymphatic drainage intraop eratively. This technique leads to a reduction of the extent of surgery in comparison with extended forms of pelvic lymphadenectomy, without having to expect a significantly reduced detection of micrometastases.

Szintillationssondengesteuerte Sentinel-Lymphadenektomie beim malignen Melanom

Summary. In cutaneous melanoma, biopsy of the first tumor-draining lymph node (Sentinel node, SLN) may replace routine elective lymph-node dissection (ELND). The SLN has been shown to contain the first micrometastasis in early lymphatic tumor dissemination. As micrometastases were identified in 10–30 % of stage I (AJCC/UICC) patients, sentinel lymphonodectomy (SLND) should enable us to select patients clinically in stages I and II, but histopathologically in stage III. This optimization of patient selection is mandatory, as only this subgroup profits from ELND. Since the beginning of 1995 we was scintillation detector (gamma probe)-guided sentinel biopsy in patients with a melanoma > 1.0 mm and clinically negative lymph nodes. After injecting colloidal 99m-Tc-labelled tin(II)-sulfide solution around the tumor (or the biopsy scar), the SLN can be localized exactly. The technique is minimally invasive and easy to handle. If the SLN contains tumor, a standard en bloc lymphonodectomy is performed. Long-term follow-up, however, is needed to delineate the role of this procedure in melanoma treatment.Zusammenfassung. Der Sentinel-Lymphknoten (SLN) entspricht dem ersten Lymphknoten, über den der Primärtumor drainiert wird, d. h. im Frühstadium einer lymphogenen Metastasierung werden in diesem Lymphknoten die ersten Mikrometastasen erwartet. Nachdem bereits im Stadium I (AJCC/UICC) des malignen Melanoms 10–30 % der Patienten Mikrometastasen in den Lymphknoten aufweisen, sollte die Sentinel-Lymphknotendissektion (SLND) eine Differenzierung jener Patienten ermöglichen, die klinisch zwar einem Stadium I und II zuzuordnen sind, pathohistologisch jedoch einem Stadium III entsprechen. Nur sie profitieren von einer elektiven Lymphknotendissektion (ELND). Seit Anfang 1995 führen wir bei Patienten mit einer Melanomdicke > 1 mm nach Breslow und klinisch freien Lymphknoten eine SLND mit Hilfe einer Szintillationsmeßsonde durch. Der betreffende Lymphknoten läßt sich exakt lokalisieren, durch eine kleine Incision gewebeschonend entfernen und seine vollständige Resektion durch eine abschließende Aktivitätsmessung im Operationsgebiet belegen. Bei histologisch nachgewiesenem Tumorbefall schließt sich eine Ausräumung der gesamten Lymphknotenregion an.

Sentinel-Lymphadenektomie beim malignen Melanom

Summary. The sentinel lymph node dissection (SLND) is one of the most striking developments in the treatment of melanoma. Since the first report by Morton et al. in 1992, the method has been refined, and its use has increased. Introduced as an alternative to elective lymph node dissection (ELND), it has rapidly made its way into clinical practice. SLND allows precise pathologic staging through removal and analysis of a limited number of nodes (false-negative rate < 2 %). It distinguishes patients with clinically occult nodal disease from those with tumor-free regional basin who would not benefit from radical dissection. However, the SLND is still an experimental procedure with yet unproven utility.Zusammenfassung. Die Sentinel-Lymphadenektomie/selektive Lymphknotendissektion (SLND) stellt eine der bedeutendsten Entwicklungen in der Melanomtherapie dar. Seit der ersten Publikation durch Morton et al. im Jahre 1992 konnte die Methode wesentlich verbessert und ihre Anwendung deutlich gesteigert werden. Als Alternative zur elektiven Lymphknotendissektion (ELND) beim Melanom eingeführt, hat sie rasch den Weg in die klinische Praxis gefunden. Das intraoperative „lymphatic mapping“ und die SLND erlauben ein präzises pathologisches Staging durch Entnahme und Analyse einer limitierten Lymphknotenanzahl (Falsch-negativ-Rate < 2 %). Sie selektionieren Patienten mit klinisch okkultem Lymphknotenbefall von jenen, die eine tumorfreie regionäre Lymphknotenregion aufweisen und erspart letzteren somit eine radikale Dissektion. Dennoch stellt die SLND eine Behandlungsstrategie dar, deren Nutzen bislang nicht bewiesen ist. Ihre klinische Bedeutung bleibt somit zunächst noch fraglich.

Mammacarcinomstaging mittels Sentinel-Lymphadenektomie

Summary. The objective of our trial was to evaluate the significance and usefulness of sentinel lymphadenectomy (SLNE) for the staging of regional lymph nodes in breast cancer patients. The study presented illustrates the method and our results. As has been documentated for melanoma, the first lymph node [sentinel node (SLN)] to receive lymphatic drainage from a primary tumor is the expected first site of lymph-node metastasis. The database presented includes 12 patients with operable breast cancer and clinically negative lymph nodes. In 11 cases the described method was applicable. In only one case was there no correlation between the histology of the SLN and the axillary specimen. Three SLN were tumor-positive. Successful completion of examination of a large number of patients with a long follow-up has the potential of reducing the number of axillary dissections and of significantly reducing morbidity in the majority of breast cancer patients.Zusammenfassung. Ziel unserer Untersuchungen ist es, die Wertigkeit und Anwendbarkeit der Sentinel-Lymphadenektomie (SLNE) im Hinblick auf das Staging der regionären Lymphknoten beim Mammacarcinom zu evaluieren. Wie für das maligne Melanom dokumentiert, stellt der 1. Lymphknoten [Sentinel-Lymphknoten (SLN)] im Lymphabflußgebiet des Primärtumors auch gleichzeitig die zu erwartende 1. Lokalisation einer möglichen Lymphknotenmetastasierung dar. Die dargestellten Ergebnisse beziehen sich auf 12 Patientinnen, wovon die beschriebene Methodik in 11 Fällen anwendbar war. Nur einmal korrelierte das histologische Ergebnis des SLN und des Axilladissektats nicht miteinander; 3 mal war der SLN carcinompositiv. Nach Vorliegen ausreichend großer Patientenzahlen und einer entsprechend langen Nachbeobachtungszeit bietet sich in Zukunft durch die SLNE evtl. die Möglichkeit, die Anzahl der zu Stagingzwecken durchgeführten axillären Lymphknotendissektionen beim Mammacarcinom deutlich zu reduzieren.

Sentinel Lymph Node Biopsy in Prostatic Cancer

The identification of lymph drainage has significant clinical importance for tumor spread in prostatic cancer. Pelvic lymph node metastases indicate a poor prognosis for patients with clinically localized prostate cancer. The prognosis depends on nodal cancer volume (1), extracapsular extension (2), and the number of prostatic nodes affected (3). It is not clear whether the more valuable prognostic factor is the diameter of the largest metastases, or the total number of positive lymph nodes (4).