Paul J. Borgstein

Reliability of intraoperative frozen section and imprint cytological investigation of sentinel lymph nodes in breast cancer

The sentinel lymph node procedure enables selective targeting of the first draining lymph node, where the initial metastases will form. A negative sentinel node (SN) predicts the absence of tumour metastases in the other regional lymph nodes with high accuracy. This means that in the case of a negative SN, regional lymph node dissection is no longer necessary. Besides saving costs, this will prevent many side‐effects of lymph node dissection. The aim of this study was to evaluate the reliability of intraoperative cytological and frozen section investigation of the SN to detect metastases. This would allow the axillary lymph node dissection to be performed in the same session as the SN procedure and the excision of the primary tumour in case of a positive SN.

Functional lymphatic anatomy for sentinel node biopsy in breast cancer: echoes from the past and the periareolar blue method.

OBJECTIVE To simplify and improve the technique of axillary sentinel node biopsy, based on a concept of functional lymphatic anatomy of the breast. SUMMARY BACKGROUND DATA Because of their common origin, the mammary gland and its skin envelope share the same lymph drainage pathways. The breast is essentially a single unit and has a specialized lymphatic system with preferential drainage, through select channels, to designated (sentinel) lymph nodes in the lower axilla. METHODS These hypotheses were studied by comparing axillary lymph node targeting after intraparenchymal peritumoral radiocolloid (detected by a gamma probe) with the visible staining after an intradermal blue dye injection, either over the primary tumor site (90 procedures) or in the periareolar area (130 procedures). The radioactive content, blue coloring, and histopathology of the individual lymph nodes harvested during each procedure were analyzed. RESULTS Radiolabeled axillary nodes were identified in 210 procedures, and these were colored blue in 200 cases (94%). The targeting concordance between peritumoral radiocolloid and intradermal blue dye was unrelated to the breast tumor location or the site of dye injection. Radioactive sentinel nodes were not stained blue in 10 procedures (5%), but this mismatching could be explained by technical problems in all cases. In two cases (1%), the (pathologic) sentinel node was blue but had no detectable radiocolloid uptake. CONCLUSIONS The lessons learned from this study provide a functional concept of the breast lymphatic system and its role in metastasis. Anatomical and clinical investigations from the past strongly support these views, as do recent sentinel node studies. Periareolar blue dye injection appears ideally suited to identify the principal (axillary) metastasis route in early breast cancer. Awareness of the targeting mechanism and inherent technical restrictions remain crucial to the ultimate success of sentinel node biopsy and may prevent disaster.

Selection of patients for resection of colorectal metastases to the liver using diagnostic laparoscopy and laparoscopic ultrasonography

OBJECTIVE To assess the value of diagnostic laparoscopy (DL) and laparoscopic ultrasonography (LUS) in the staging and selection of patients with colorectal liver metastasis. SUMMARY BACKGROUND DATA Preoperative imaging modalities such as ultrasound, computed tomography, and magnetic resonance imaging are limited in the assessment of the number and exact location of hepatic metastases and in the detection of extrahepatic metastatic disease. Consequently, the surgeon is often faced with a discrepancy between preoperative imaging results and perioperative findings, resulting in either a different resection than planned or no resection at all. METHODS Fifty consecutive patients were planned for DL and LUS in a separate surgical sitting to assess the resectability of their liver metastases. All patients were considered to be candidates for resection on the basis of preoperative imaging studies. RESULTS Laparoscopy could not be performed in 3 of the 50 patients because of dense adhesions. The remaining 47 patients underwent DL. On the basis of DL and LUS, 18 (38%) patients were ruled out as candidates for resection. Of the 29 patients who subsequently underwent open exploration and intraoperative ultrasonography, another 6 (13%) were deemed to have unresectable disease. CONCLUSIONS The combination of DL and LUS significantly improves the selection of candidates for resection of colorectal liver metastases and effectively reduces the number of unnecessary laparotomies.

Pathological investigation of sentinel lymph nodes

Abstract. The sentinel lymph-node procedure enables selective targeting of the first draining lymph node, where the initial metastases will form. A negative sentinel node (SN) predicts the absence of tumour metastases in the other regional lymph nodes with high accuracy. This means that in the case of a negative SN, regional lymph-node dissection is no longer necessary. Besides saving costs, this will prevent many side-effects as a result of lymph-node dissection. The task of the pathologist is to screen SNs for metastases. To this end, several techniques are available such as standard histo- and cytopathological techniques, immunohistochemistry, flow cytometry, and molecular biological techniques. These methods are explained and their sensitivity for detecting SN metastases is discussed. Some of these techniques also appear to be useful for intra-operative evaluation of SNs. The standard protocol for detection of SN metastases consists of extensive histopathological investigation including step H&E stained sections and immunohistochemistry. Intra-operative frozen-section analysis of SNs has been shown to be reliable for breast-cancer axillary lymph nodes. In the intra-operative setting, imprint cytology can also be used but its additional value to frozen section analysis is not yet clear. Further studies are necessary to establish the role of sophisticated molecular biological techniques such as reverse transcription polymerase chain reaction (RT-PCR) in detecting SN metastases. The sensitivity of flow cytometry is too low for this purpose.

Sentinel Node Biopsy in Melanoma Patients: Dynamic Lymphoscintigraphy Followed by Intraoperative Gamma Probe and Vital Dye Guidance

Abstract. Biopsy of the first tumor-draining lymph node (sentinel node, SN) is bound to become the procedure of choice in regional staging of melanoma patients. A tumor-negative SN virtually excludes lymphatic metastases and obviates the need for lymph node dissection. The aim of this study was to combine the advantages of three known techniques to improve the yield of successful SN biopsies. A total of 150 drainage areas in 135 patients was evaluated. First, preoperative dynamic and static lymphoscintigraphy was performed after injection of technetium 99m colloidal albumin. In all patients one to three focal accumulations, concordant with SNs, were seen in the lymphatic drainage areas, in 97% within 20 minutes from injection of the tracer. Peroperative identification of the SN, 2 to 24 hours after injection of the tracer, was done with a handheld gamma probe to estimate the optimal site for the small incision and to guide preparation. Vital dye was injected just preoperatively and served to facilitate the final identification and biopsy of the SN. A total of 216 SNs were biopsied. Micrometastases were found in 39 SNs in 30 drainage areas, and in 22 of the 30 the SN was the only node harboring tumor. In 5 of 30 drainage areas, the SN did not contain blue dye and would not have been found without the gamma probe. Up to now (follow-up 233–691 days) no recurrence has developed in the lymphatic drainage areas where the SN was tumor-free. It was concluded that by combining these three techniques the SN could be detected and excised in all patients. The procedure combines a steep learning curve with high sensitivity.

Reliability of the Sentinel Node Procedure in Melanoma Patients: Analysis of Failures After Long-Term Follow-Up

Background: The sentinel node (SN) concept assumes that early lymphatic metastases, if present, always are found first in the SN. The aim of this study was to determine the reliability ofthis procedure by establishing the success rate and number of failed procedures during a follow-up period of at least 2 years.Methods: From August 1993 to November 1996, 204 consecutive patients with stage I and II cutaneous melanoma underwent SN biopsy by a triple technique. Preoperatively, all patients underwent (dynamic) lymphoscintigraphy. A gamma probe and blue dye helped localize the SN(s) during surgery, and these nodes subsequently were excised. These lymph nodes were step-sectioned and examined by routine and immunohistochemical staining. If the SN contained tumor cells, a lymphadenectomy was performed at a later date.Results: The median follow-up time was 42 months. The success rate was 99%. Three patients developed a recurrence in the negative SN basin during follow-up, without simultaneous appearance of (locoregional) metastases.Conclusions: With a 99% success rate and a 1.5% rate of failed SN procedures (7% falsenegative rate) after a median follow-up of 3.5 years, we concluded that the combined triple technique approach of detecting the SN was a reliable method to accurately identify and retrieve the SN.

Ultrasound-guided lumpectomy of nonpalpable breast cancers : A feasibility study looking at the accuracy of obtained margins

Complete excision of a nonpalpable breast cancer after wire localization is a difficult procedure. Often, adequate margins are not obtained, and a second procedure is then required. Prospectively, we studied the feasibility of ultrasound‐guided excisions of nonpalpable breast cancers, with particular attention to the accuracy of the procedure in obtaining adequate margins.

Are locoregional cutaneous metastases in melanoma predictable

Background: In-transit metastases and satellite lesions are manifestations of locoregional cutaneous recurrence that are characteristic of malignant melanoma. They are the result of tumor cell emboli entrapped in the dermal lymphatics between the primary tumor and the regional lymph node basin. Histopathological features of lymphatic invasion were investigated to determine the possibility of predicting locoregional cutaneous metastases in melanoma patients.Methods: In a prospective study, 258 patients with clinical stage I melanoma underwent wide local excision and sentinel node biopsy. Nodal metastases were found in 53 (21%) patients. Of 29 patients (11.2%) who had developed recurrences to date, 17 (6.6%) had locoregional cutaneous metastases. All surgical specimens were examined with particular attention to histopathological signs of lymphatic vascular invasion or microscopic satellites.Results: Unequivocal signs of lymphatic invasion were observed in 14 of 258 patients (5.4%), and 13 (93%) of these patients subsequently developed in-transit metastases, after a median interval of 10 months. The primary melanoma was located on the extremities in seven patients. The median Breslow thickness was 2.5 mm, and 5 showed ulceration. In 244 of 258 patients (94.6%), there were no signs of lymphatic invasion. To date, only four patients (1.6%) have had a locoregional cutaneous recurrence, occurring after a median interval of 29 months. All four of these patients had ulcerative melanomas on an extremity, with a median thickness of 4.0 mm. The presence of lymphatic invasion was significantly related to early locoregional cutaneous relapse (P _ .0001).Conclusions: Locoregional cutaneous recurrence appears to be highly predictable in the presence of histopathological signs of lymphatic invasion. Lymphatic invasion is an important prognostic parameter and should be included as a stratification criterion when selecting patients for adjuvant (locoregional) therapy.

The sentinel node procedure in cutaneous melanoma: an overview of 6 years’ experience

The utility of elective lymph node dissection (ELND) in patients with cutaneous melanoma has been one of the most debated controversies in surgical oncology for decades. The sentinel node (SN) concept has probably ended this discussion. The opponents of ELND argued that no evidence had been provided to support ELND and that too many patients had been subjected to surgery from which they derived no benefit and which even entailed significant morbidity, such as long-term lymphoedema [1]. A few randomized prospective trials showed no benefit of ELND with regard to disease-free survival rate or overall survival rate [2–4]. Therefore, a “wait and see” policy was advocated until clinically detectable metastases developed in the regional lymph nodes, whereupon a regional lymph node dissection was performed. On the other hand a recent study showed that patients with a melanoma on the trunk with clinically negative nodes but histologically positive nodes at ELND had a better prognosis than patients who developed node metastases during follow-up and underwent delayed regional node dissection [6]. In addition, a few non-randomized retrospective trials have suggested a small but significant therapeutic benefit from ELND, especially in patients with micrometastases [7–9]. Node dissection may thus offer increased survival in patients with micrometastases. Consequently, the SN procedure may further improve the prognosis in this group of patients [10]. The SN concept is based on the theory of an orderly progression of tumour cells within the lymphatic system. The route of metastasis to regional lymph nodes can be predicted by following the lymph flow from the primary tumour site to the first draining node, the SN, within the regional lymphatic drainage area. The SN concept assumes that early lymphatic metastases, if present, are invariably first found in the SN. A negative SN biopsy would preclude the presence of lymphatic malignant involvement and thus avoid the necessity of a total lymph node dissection with the accompanying morbidity. This technique of nodal staging is also a method to identify populations of patients who are highly susceptible to recurrence and therefore potential candidates for adjuvant therapy in the future [11]. The purpose of this article is to survey the worldwide history and experience with the SN procedure since Morton et al.’s report in 1992 [10]. The technique is described, and its validity and the variables that influence its success are considered. The staging function of the procedure and its potential role in respect of the use of adjuvant therapy are also addressed.

In-transit lymph node metastases in breast cancer: a possible source of local recurrence after Sentinel Node procedure

Aims: In-transit lymph node metastases are a common phenomenon in melanoma patients and have been increasingly recognised since the introduction of the Sentinel Node (SN) procedure. To which extent this also occurs in patients with breast cancer has not been studied yet. The aim of this study was therefore to explore the occurrence of in-transit lymph node metastases in patients with breast cancer. Methods: Afferent lymph vessels to the SN identified by blue dye were removed from 17 patients with breast cancer during a regular SN procedure. Results: Three out of 17 patients showed a lymph node associated with the afferent lymph vessel. One of these lymph nodes showed a breast cancer macrometastasis, to be regarded as an in-transit metastasis. This metastasis would normally have been left in situ. Conclusions: In-transit lymph nodes associated with the afferent SN lymph vessels seem to occur in a significant proportion of patients with breast cancer. These lymph nodes may contain metastases, which are a potential source of local recurrence when left in situ. This finding generates the hypothesis that there may be an indication to remove these lymph vessels during the SN procedure.