Vital dyes in sentinel node localization

Vital blue dyes were used to show the feasibility and accuracy of intraoperative lymphatic mapping of the sentinel node (SN) in patients with melanoma, breast cancer, and other solid tumors. Surgeons who have successfully completed an adequate number of cases of intraoperative mapping and sentinel lymph node dissection (SLND) can use blue dye alone to localize the SN. However, radiopharmaceutical agents can facilitate intraoperative mapping; preoperative lymphoscintigraphy can identify the location of the SN, and intraoperative mapping with the gamma probe can provide an auditory signal that complements the visual guide provided by the blue dye. Studies are required to establish more clearly the intralymphatic kinetics of the various radiopharmaceutical agents. An ongoing international Phase III trial in melanoma, the 2 upcoming trials in breast cancer, and similar trials for other solid tumors will further clarify the future role of SLND.     

Use of lymphoscintigraphy with SPECT/CT for sentinel node localization in a case of vaginal melanoma

A 45-year-old woman with vaginal melanoma underwent Tc-99m sulfur colloid (filtered) lymphoscintigraphy with the acquisition of planar and SPECT/CT images for localization of a sentinel node before surgery. The study identified both inguinal and perirectal sentinel nodes, which proved beneficial in mapping potential anatomic spread of disease for staging and therapy planning. These results provide evidence for the use of routine SPECT/CT imaging for pelvic lymphoscintigraphic studies or as an adjunct tool for localizing sentinel nodes in cases that would not be demonstrated with planar imaging alone.     

Limited pelvic lymphadenectomy using the sentinel lymph node procedure in patients with localised prostate carcinoma: a pilot study

Purpose The purpose of this study was to determine the potential role of the sentinel lymph node (SLN) procedure in limited lymph node dissection in patients with apparently localised prostate carcinoma.Methods In 27 patients with organ-confined prostate cancer, a single injection of 0.3 ml/30 MBq ^99mTc-rhenium sulphur colloid was injected transrectally into the peripheral zone of each lobe of the prostate (total 0.6 ml/60 MBq) under ultrasound guidance. Two hours after injection, scintigraphy was performed. The first step in surgery was the detection and dissection of lymph nodes identified as SLNs. Then, standard lymphadenectomy was performed, consisting in a limited dissection that included all lymph nodes from the obturator fossa and along the external iliac vein. Lymphatic tissue along the hypogastric artery was not systematically removed, except in the presence of SLNs.Results Mean patient age was 66 years (48–77); the mean serum prostate-specific antigen value was 10.6 ng/ml. In a high proportion of patients (21/27, 77.8%) an SLN was located along the initial centimetres of the hypogastric artery. The second most frequent site of SLNs was in the obturator fossa (11/27 patients, 40.7%), followed by the external iliac area (5/27 patients, 18.5%). Four patients had lymph node metastases, all in SLNs: two in the hypogastric area and two in the obturator fossa. Conclusion The SLN procedure revealed the individual variability in the lymphatic drainage of the prostate. The main site of SLNs was the hypogastric area, and two of the four metastatic nodes were located at this site. A limited standard pelvic lymphadenectomy, excluding the hypogastric lymph nodes, would have missed half of the lymph node metastases in this study. A radionuclide SLN procedure could assist in the correct staging of patients with early prostate cancer, especially when performing limited lymphadenectomy.     

The concept of sentinel node localization: how it started

Intraoperative lymphatic mapping and sentinel lymphadenectomy (LM/SL) followed by selective complete lymphadenectomy (SCLND) has revolutionized the management of the regional lymph node basin in patients with solid tumors. Many investigators over the centuries have contributed to the understanding of the progression of tumor cells through the lymphatic system. This article discusses the conceptual background for the development of LM/SL in the original model of melanoma. The sentinel node hypothesis has been validated by a multicenter clinical trial showing that LM/SL in melanoma can be accurately performed in a uniform manner by multidisciplinary teams at cancer centers worldwide. Although the diagnostic and prognostic accuracy of LM/SL has been established, demonstration of the therapeutic use of this procedure awaits analysis of survival data from the multicenter randomized trial of wide excision alone versus wide excision plus LM/SL/SCLND.     

Factors affecting sentinel node localization during preoperative breast lymphoscintigraphy.

Variable success rates for identifying axillary (AX) sentinel nodes in breast cancer patients using preoperative lymphoscintigraphy have been reported. We evaluated the effects of age, weight, breast size, method of biopsy, interval after biopsy, and imaging view on the success of sentinel node identification and on the kinetics of radiopharmaceutical migration. METHODS: Preoperative breast lymphoscintigraphy was performed in consecutive breast cancer patients from February 1998 to December 1998. The ipsilateral shoulder was elevated on a foam wedge and the arm was abducted and elevated overhead. Imaging using this modified oblique view of the axilla (MOVA) started immediately after peritumoral injection of Millipore-filtered 99mTc-sulfur colloid and continued until AX sentinel nodes were identified. Anterior views were obtained after MOVA. AX, internal mammary (IM), and clavicular (CL) basins were monitored in all patients. MOVA was compared with the anterior view for sentinel node identification. Age, weight, breast size, method of biopsy, interval after biopsy, and primary tumor location were evaluated for their effects on sentinel node localization and transit times from injection to arrival at the sentinel nodes. RESULTS: Seventy-six lymphoscintigrams were obtained for 75 patients. AX sentinel nodes were revealed in 75 (99%) cases. IM or CL sentinel nodes were found in 19 (25%) cases and were not related to tumor location; exclusive IM drainage was present in 1 (1%) case. Identification of AX sentinel nodes was equivalent with MOVA and anterior views in 18 (24%) patients, was better with MOVA in 20 (26%) patients, and was accomplished only with MOVA in 38 (50%) patients. Median transit time was 17.5 min (range, 1 min to 18 h) after injection, and larger breast size was associated with increased transit time. No effect of age, weight, biopsy method, interval from biopsy, or tumor location on transit time was found. CONCLUSION: Use of MOVA can improve identification of AX sentinel nodes. Although AX drainage is the predominant pattern, a tumor in any portion of the breast can drain to IM sentinel nodes. Transit time was influenced by breast size. Overall short arrival times with this technique allow sentinel lymph node dissection to be performed on the same day as lymphoscintigraphy.     

Computed tomography lymphography with intrapulmonary injection of iopamidol for sentinel lymph node localization

PURPOSE: Experimental and clinical evaluation of the potential utility of indirect computed tomographic lymphography (CT-LG) with intrapulmonary injection of iopamidol for preoperative localization of sentinel lymph node station in non-small cell lung cancer. METHODS: CT-LG with intrapulmonary injection of 0.5 mL of undiluted iopamidol was performed in 10 dogs using a multidetector-row CT unit, followed by postmortem examination of enhanced lymph nodes in 5 of these dogs. The CT-LG with peritumoral injection of 1 mL of the contrast agent was also performed in 9 patients with non-small cell lung cancer without lymphadenopathy. At surgery, enhanced lymph nodes were resected under CT-LG guide, followed by standard lymph node dissection with macroscopic and histologic examination. A significant enhancement of lymph nodes was determined when CT attenuation value was increased with 30 Hounsfield units (HU) compared with precontrast images. RESULTS: CT-LG visualized a total of 15 enhanced lymph nodes (on average, 1.5 nodes per animal) within 2 minutes after contrast injection in the 10 dogs, with average size of 6.7+/- 1.9 mm and average maximum CT attenuation of 149 +/- 41 HU. All the 8 enhanced nodes in 5 dogs were found in the appropriate anatomic locations in postmortem examinations. Without noticeable complications, CT-LG visualized 30 ipsilateral intrathoracic lymph nodes including 19 hilar/pulmonary and 11 mediastinal nodes in the 9 patients (on average, 2.2 hilar/pulmonary and 1.1 mediastinal nodes per patient) within 2 minutes after contrast injection, with average size of 4.7+/- 0.4 mm and average maximum CT attenuation of 134 +/- 52 HU. At surgery, all these enhanced nodes could be accurately found and resected under CT-LG guidance. Metastasis was not evident in either of these enhanced lymph nodes or the remaining distant nodes in all patients. CONCLUSION: Quick and accurate localization of sentinel lymph node station on detailed underlying lung anatomy by using indirect CT-LG may be of value to guide selective lymph node dissection for minimally invasive surgery in non-small cell lung cancer.     

One-day or two-day procedure for sentinel node biopsy in melanoma?

Purpose  We compared the outcome of a 1-day and a 2-day sentinel node (SN) biopsy procedure, evaluated in terms of lymphoscintigraphic, surgical and pathological findings. Methods  We studied 476 patients with melanoma from two melanoma centres using static scintigraphy and blue dye. A proportional odds model was used for statistical analysis. Results  The number of SNs visualized at scintigraphy increased significantly with time from injection to scintigraphy and activity left in the patient at scintigraphy, and depended on the melanoma location. The number of SNs removed at surgery increased with the number of SNs visualized at scintigraphy and time from injection to surgery. The frequency of nodal metastasis increased with increasing thickness and Clark level of the melanoma, and was highest for two SNs visualized at scintigraphy. Conclusion  This study showed that early vs. late imaging and surgery do make a difference on the outcome of the SN procedure and confirmed the importance of the scintigraphic visualization of all true SNs.     

乳腺癌前哨淋巴结的定位及诊断的影像研究进展

前哨淋巴结(SLN)对于判断早期乳腺癌病人腋窝淋巴结状态具有重要临床意义。超声、CT、MRI技术与间接淋巴造影术联合可以显示淋巴管道,通过捕捉淋巴管道及淋巴结之间的关系可对SLN定位,特别是MR联合间接淋巴造影术为SLN的定位及诊断提供了新的思路。     

Gamma probe sentinel node localization and biopsy in breast cancer patients treated with a neoadjuvant chemotherapy scheme

The aim of this study was to analyse the accuracy of scintigraphic and gamma probe sentinel node (SN) localization in breast cancer patients who have been submitted to neoadjuvant chemotherapy (NC). Seventy-six patients with single breast cancer were included in the study, and were classified into two groups. Group 1 consisted of 40 women who had received NC, and Group 2 consisted of 36 women who did not receive NC. All patients received 111 MBq (3 mCi) of 99Tcm-nanocolloid in 3 ml, by peritumoural injection. Anterior and lateral thoracic scans were obtained 2 h post-injection. The following day (18-24 h post-injection) the patients underwent surgery and sentinel nodes were localized by using a gamma probe. Complete axillary lymph node dissection was performed in all patients. Histological analysis included haematoxylin-eosin in all cases and immunohistochemistry in 10 cases. In Group 1, SNs were localized in 36/40 patients, histological analysis was performed in 34 and there were four false negatives (22%). In Group 2, SNs were localized in 32/36 patients, histological analysis was performed in 29 and there were two false negatives (9%). Predictive negative values were 78% and 90% in Groups 1 and 2, respectively. In summary, sentinel node localization in breast cancer patients submitted to previous neoadjuvant chemotherapy is less accurate than in patients who do not receive this therapy. The procedure is not sufficiently accurate to localize the sentinel node, thus it cannot be recommended in these patients.     

Feasibility of sentinel node detection in renal cell carcinoma: a pilot study

Purpose  

Lymphatic drainage from renal cell carcinoma is unpredictable and the therapeutic benefit and extent of lymph node dissection are controversial. We evaluated the feasibility of intratumoural injection of a radiolabelled tracer to image and sample draining lymph nodes in clinically non-metastatic renal cell carcinoma.     

Preoperative radionuclide lymphangiography and sentinel node localization with radionuclide techniques. Advantages and ambiguous aspects

Axillary lymph node status is one of the most important prognostic factors for patients with melanoma and early breast cancer. Axillary lymph node dissection is an important part of the surgical treatment of breast cancer. As an alternative to axillary node dissection was proposed the sentinel lymph node detection (SLND). This technique was initially described for detecting occult lymph node metastasis in patients with melanoma and recently is used for breast cancer patients. Nowadays the radioisotopique techniques, including the lymphoscintigraphy and the intraoperative detection of SN, have received attention as a possible alternative to axillary lymph nodes dissection because of the clinical value of SN in malignancies and the development of technical equipment. We review the different techniques of preoperative lymphoscintigraphy and intraoperative detection of SN, including the radioisotopique tracers, timing and site of injection and the clinical value of both methods in patients with early breast cancer.     

Innovation in early breast cancer surgery: radio-guided occult lesion localization and sentinel node biopsy

The surgical management of non-palpable breast lesions remains controversial. At the European Institute of Oncology we have introduced a new technique, radio-guided occult lesion localization (ROLL) to replace standard methods and overcome their disadvantages. Regarding axillary dissection, probe-guided biopsy of the sentinel node (SN) is easy to apply, and the whole procedure is associated to a low risk of false negatives. We suggest that the SN technique should be widely adopted to stage the axilla in patients with breast cancer with clinically negative lymph nodes. Large-scale implementation of the sentinel node technique will reduce the cost of treatment as a result of shorter hospitalization times.     

Lymph node wire localization post-chemotherapy: Towards improving the false negative sentinel lymph node biopsy rate in breast cancer patients

PurposeTo evaluate whether the disease status of the pre-neoadjuvant chemotherapy (NAC) core biopsied lymph node (preNACBxLN) in patients with node positive breast cancer corresponds to nodal status of all surgically retrieved lymph nodes (LNs) post-NAC and whether wire localization of this LN is feasible.Materials and methodsHIPPA compliant IRB approved retrospective study including breast cancer patients (a.) with preNACBxLN confirmed metastases, (b.) who received NAC, and (c.) underwent wire localization of the preNACBxLN. Electronic medical records were reviewed. Fisher's exact test was used to compare differences in residual disease post-NAC among breast cancer subtypes.Results28 women with node positive breast cancer underwent ultrasound guided wire localization of the preNACBxLN, without complication. There was no evidence of residual nodal disease for 16 patients, with mean 4.4 (median 4) LNs resected. 12 patients had residual nodal metastases, with mean 9.2 (median 7) LNs resected and mean 2.3 (median 2) LNs with tumor involvement. 11 patients had metastases detected within the localized LN. One patient had micrometastasis in a sentinel LN, despite no residual disease in the preNACBxLN. Patients with luminal A/B breast cancer more often had residual nodal metastases (86%) at pathology, as compared to patients with HER2 + (20%) and Triple Negative breast cancer (50%), though not quite achieving statistical significance (p = 0.055).ConclusionUltrasound guided wire localization of the preNACBxLN is feasible and may improve detection of residual tumor in patients post-NAC.     

Contribution of SPECT/CT for sentinel node localization in patients with ipsilateral breast cancer relapse

Background

In recent years repeat sentinel node (SN) biopsy has been proven to be feasible in local breast cancer recurrence (LBCR). However, in these patients SNs outside the ipsilateral axilla are frequently observed. This study evaluates the contribution of SPECT/CT for SN localization and surgical adjustment in LBCR patients.

Methods

SN biopsy was performed in 122 LBCR patients (median age 60.5 years, range 24–87), enrolled from August 2006 to July 2015. Median disease-free time lapse was 109.5 months (range 9–365). Axillary lymph node dissection (ALND) had previously been performed in 55 patients, SN biopsy in 44, both techniques in 13 and fine-needle aspiration in 10. Primary breast cancer treatment included radiotherapy in 104 patients (85.3 %) and chemotherapy in 40 (32.8 %). Preoperative lymphatic mapping, using planar scintigraphy (PS) and SPECT/CT included report of SN location according to lymph node territory. In case of a territorial PS-SPECT/CT mismatch, surgery was adjusted according to SPECT/CT findings.

Results

SPECT/CT SN visualization rate was higher than PS (53.3 % vs. 43.4 %, p n.s.). PS-SPECT/CT territory mismatch, found in 60 % (39/65) of patients with SN visualization, led to surgical adjustment in 21.3 % (26/122) of patients. The SN procedure was finally performed in 104 patients resulting in a 65.7 % surgical retrieval rate with a total of 132 removed SNs (1.86/patient). SN metastases were found in 17/71 patients (23.9 %), in 16 of them (94 %) in ipsilateral basins outside the axilla or in the contralateral axilla.

Conclusion

Using SPECT/CT there is a trend to visualize more SNs in LBCR, providing at the same time important anatomical information to adjust intraoperative SN procedures. The addition of SPECT/CT to the standard imaging protocol may lead to better staging mainly in patients presenting drainage outside the ipsilateral axilla.

     

Towards quality assurance of the sentinel node procedure in malignant melanoma patients: a single institution evaluation and a european survey

The status of the regional lymph node (LN) is a critical component in staging patients with malignant melanoma. Biopsy of the first tumour-draining LN (sentinel node, SN) may replace routine elective LN dissection. However, until now, the applied methods have differed widely. Therefore, the aim of this study was to formulate recommendations for the pre-operative identification and intra-operative retrieval of the SN. We present the results of an independent survey of the clinical practice of the SN procedure via a postal questionnaire among 136 nuclear physicians in different institutes throughout 16 European countries. Moreover, the results of the SN procedure in our institution in an open prospective intervention trial in 80 patients with malignant melanoma without palpable LNs are also presented. In our protocol, on average, 6 h prior to surgery, 80 MBq technetium-99m nanocolloid was injected intracutaneously around the circumference of the diagnostic excision scar of the primary melanoma. No additional blue dye procedure was used to judge the accuracy of the radioguided SN procedure on its own. For successful identification of the radiolabelled SN, dynamic and static images were performed and the skin projection of the detected SN was marked with a cobalt-57 source. For intra-operative mapping a hand-held gamma probe was used. Forty of the 83 respondents of the European-wide questionnaire (48%) performed the SN procedure. Although many different regimens are used, the following recommendations could be deduced for the SN procedure in patients with malignant melanoma and non-palpable LNs: (1) local, intradermal injection of 40 MBq ^99mTc-nanocolloid around the diagnostic excision scar of the primary melanoma; (2) two-phase LS: dynamic imaging (20 frames of 60 s, 128×128 matrix, LEAP collimator) followed by static images 1–2 h later (180 s per record); (3) intra-operative retrieval of the SN with a gamma probe; (4) histopathological examination of the SN on serial sections. In our trial, surgical retrieval of the SN was successful in 95% of the cases. Dynamic lymphoscintigraphy (LS) contributed to the SN procedure by showing anatomically unpredictable lymph flow to extra-regional SNs (10% of the patients in this study) and multiple SNs. Of the 77 retrieved SNs, 13 contained metastatic disease (17%). Consequently, these patients underwent a formal LN dissection of the affected basin. In conclusion, the SN concept is a rational approach to select patients who could, theoretically, benefit from early LN dissection of the affected basin. Standardisation of the SN procedure will improve the results of this approach, and could be useful for quality control and for making comparisons with other countries in coming years. Received 28 October 1998