Intraoperative Sentinel Node Identification Research Articles

Preliminary study of indirect CT lymphography-guided sentinel lymph node biopsy in a tongue VX2 carcinoma model

The feasibility of using indirect CT lymphography (CT-LG) to guide sentinel lymph node (SLN) biopsy in a rabbit model of tongue VX2 carcinoma with cervical lymph node metastasis was studied. Tongue VX2 carcinoma with cervical lymph node metastasis was induced in 19 rabbits by injecting VX2 carcinoma suspension into the tongue submucosa. SLN biopsy was performed under the guidance of indirect CT-LG. SLN identification was performed by indirect CT-LG combined with blue dye injection in 2 rabbits. Tongue SLNs were identified preoperatively by indirect CT-LG and blue-stained SLNs were visualized intraoperatively. Only one SLN was enhanced in each side of the neck, lateral to the larynx-tracheal region. CT attenuation values of the enhanced SLNs were 782.4+/-46.6, 443.1+/-68.5, 180.3+/-20.6 and 80.5+/-10.7 HU at 1, 5, 15 and 20 min after contrast injection. Overall, ipsilateral SLN identification rate was 97.4% and contralateral SLN identification rate was 100%. Ipsilateral SLN metastasis was verified in all rabbits (100%), bilateral SLN metastasis occurred in 8 rabbits (42%), and micrometastasis was found in 3 rabbits (16%). Indirect CT-LG may be useful for guiding SLN biopsies in tongue cancer. Combining indirect CT-LG with blue dye injection may improve preoperative and intraoperative SLN identification.

Value of SPECT/CT for Detection and Anatomic Localization of Sentinel Lymph Nodes Before Laparoscopic Sentinel Node Lymphadenectomy in Prostate Carcinoma

Laparoscopic evaluation of sentinel nodes is useful for staging prostate cancer, but preoperative localization of deep abdominal sentinel nodes with planar lymphoscintigraphy is difficult. We evaluated the value of SPECT/CT for detecting and localizing sentinel nodes in prostate cancer. (99m)Tc-nanocolloid was injected peri- and intratumorally, guided by transrectal ultrasonography, in 46 patients with prostate cancer of intermediate prognosis. Patients underwent planar imaging after 15 min and 2 h, SPECT/CT after 2 h, and laparoscopic sentinel node lymphadenectomy on the same day. SPECT was fused with CT and analyzed using 2-dimensional orthogonal slicing and 3-dimensional volume rendering. We evaluated the number of extra sentinel nodes found by SPECT/CT, the number of sentinel nodes found by SPECT/CT outside the area of the extended pelvic lymphadenectomy, and the anatomic information provided by SPECT/CT. Furthermore, we classified the value of the additional SPECT/CT images into 3 categories (no advantage, presumable advantage, and definite advantage) according to the extra anatomic information given and whether additional sentinel nodes were found by SPECT/CT. The patients had a mean age of 64 y (range, 53-74 y) and received a mean injected dose of 218 MBq (range, 147-286 MBq). The sentinel node visualization rate was 91% (42 patients) for planar imaging and 98% (45 patients) for SPECT/CT. In 29 of the 46 patients (63%), SPECT/CT revealed additional sentinel nodes (especially lymph nodes near the injection area) not seen on planar imaging. In 7 patients, those additional sentinel nodes were positive for metastasis (being the exclusive metastatic sentinel node in 4 patients). Overall, 15 patients (33%) had positive sentinel nodes. Sentinel nodes outside the area of extended pelvic lymphadenectomy were found in 16 patients (35%), whereas in 56% of these patients those nodes were not seen on planar imaging. Performing SPECT/CT had no advantage in 13% of the patients, a presumable advantage in 24%, and a definite advantage in 63%. Urologic surgeons used the SPECT/CT images to guide their trocar insertion sites and sentinel node finding with the probe. More sentinel nodes can be detected with SPECT/CT than with planar imaging alone. In comparison with planar imaging, SPECT/CT especially reveals extra sentinel nodes near the prostate and outside the area of the extended pelvic lymphadenectomy. Furthermore, the modality provides useful additional information about the anatomic location of sentinel nodes within and outside the pelvic area, leading to improved intraoperative sentinel node identification.

Modification of lymphoscintigraphic sentinel node identification before and after excisional biopsy of primary cutaneous melanoma

The aim of this study was to determine whether excision biopsy and primary closure of primary cutaneous melanoma modifies lymphatic drainage and accuracy of sentinel node biopsy. Thirty patients with 31 cutaneous melanomas were prospectively enrolled to undergo lymphoscintigraphy (LS) before and after excision biopsy. Tc-human serum albumin nanocolloid was first injected intradermally around the primary tumor and subsequently, after excision biopsy, adjacent to the scar. Sentinel nodes were identified by preoperative LS and the gamma-probe. Patent Blue V dye was injected intraoperatively before sentinel node biopsy. Intraoperative sentinel node identification was 100%. In 23 of 31 cases, both LSs were concordant in terms of nodal basins visualized. Two patients had a basin downstaged and six patients had a basin upstaged by the second LS. Only 50% of LS hot nodes stained blue (42 of 84). In 24 of 31 cases, the sentinel node was negative for metastases. Seven patients underwent complete lymph node dissection because of sentinel node positivity. Only one patient had metastases also to a non-sentinel node. After a median follow-up of 30 months lymph node metastases have not been observed in the eight discordant cases. This study shows that sentinel node identification and biopsy after lymphatic mapping is accurate after excision biopsy of primary cutaneous melanoma. Excision biopsy may, however, modify lymphatic drainage and a narrow excision margin should be performed if melanoma is suspected.

Sentinel node identification in clinical stage Ia non–small cell lung cancer by a combined single photon emission computed tomography/computed tomography system

A gamma probe can identify sentinel nodes before nodal dissection in the mediastinum but not in the hilum, owing to high radioactivity from primary tumors. We evaluated the utility of fused single photon emission computed tomography/computed tomography (SPECT/CT) images for the identification of sentinel nodes in the hilum for patients with clinical stage Ia non-small cell lung cancer. Technetium-99m tin colloid was injected into the peritumoral region approximately 18 hours before surgery in 63 patients with clinical stage Ia non-small cell lung cancer. On the morning of the operation, approximately 16 hours after administration of tin colloid, sentinel nodes were identified by fused SPECT/CT; this was followed by intraoperative sentinel node identification in the dissected lymph nodes by gamma probe. Because the gamma probe is a standard method for sentinel node identification, the sensitivity of fused SPECT/CT images was examined on the basis of the data of the gamma probe. Fused SPECT/CT images could identify sentinel nodes at segmental and lobar lymph nodes with a sensitivity of 0.87 and 0.74, both of which were significantly higher than 0.40 in the mediastinum (P < .001 and P = .012, respectively). In 5 patients with pathologic N1 or N2 disease, both SPECT/CT and the gamma probe could identify sentinel nodes with metastases. SPECT/CT could identify sentinel nodes of the hilum especially in segmental and lobar lymph nodes but not in the mediastinum. Because the gamma probe can identify sentinel nodes before nodal dissection in the mediastinum but not in the hilum, a combination of SPECT/CT and the gamma probe can be used to identify sentinel nodes before nodal dissection in both the hilum and the mediastinum, which will enable sentinel node navigation surgery in non-small cell lung cancer.

A second radioisotope injection enhances intraoperative sentinel node identification in breast cancer patients without visualized nodes on preoperative lymphoscintigraphy

To evaluate the influence of a second radioisotope injection on the intraoperative success rate in patients with non-visualized axillary sentinel nodes (SN). Altogether, 534 consecutive breast cancer patients with lymphoscintigraphy (LS) and SN biopsy and were included. An intratumoral injection of 99mTc-labeled human albumin colloid with a median dose of 93 MBq was applied. Forty-two of the 80 patients without axillary hot spots on LS received a second tracer injection with a median dose of 70 MBq. The visualization rate of axillary SN was 454/534 (85%). The intraoperative SN identification rate was 97% in patients with and 69% in patients without visualized SN in the axilla (P<0.00005), but the success rate was higher (88%) with a second radioisotope injection than without it (47%; P<0.0002). The failure rate in intraoperative SN identification was minimized using a second radioisotope injection in patients without axillary SN on LS.

Comparison of recurrence after vulvectomy and lymphadenectomy with and without sentinel node biopsy in early stage vulvar cancer

Objectives. To determine the usefulness of sentinel lymph node biopsy in early stage vulvar cancer and to assess recurrences after surgical treatment with sentinel node identification or surgical treatment without sentinel node identification. Methods. We reviewed the records of 55 patients with early stage vulvar cancer operated on between 1995 and 2005. A prospective series of 28 patients who underwent vulvectomy and lymphadenectomy with intraoperative sentinel lymph node identification between 2000 and 2005 (SLN group) was compared with a retrospective series of 27 patients who underwent vulvectomy and lymphadenectomy without sentinel node procedure between 1995 and 2000 (non-SLN group). Patients in the sentinel node identification group underwent preoperative lymphoscintigraphy (technetium-99 colloid albumin injection around the tumor) and intraoperative mapping with isosulfan blue dye. Results. In the SLN group, 9 tumors were T 1 and 19 were T 2, with a total of 40 groins dissected and 9 positive nodes in 7 patients. Sixty-two sentinel lymph nodes were detected with a mean of 2.2 sentinel nodes per patient (range 0–4). A false negative case was found. In the non-SLN group, 7 tumors were T 1 and 20 were T 2, with a total of 49 groins dissected and 9 positive nodes in 6 patients. Recurrence occurred in 8 patients (28.6%) in the SLN group and in 6 (26.9%) in the non-SLN group ( P = 0.8). Conclusions. Sentinel lymph node identification in early stage vulvar cancer is a feasible. Analysis of recurrence may allow considering this procedure as a possible alternative to inguino-femoral lymphadenectomy.

Intraoperative, Radio-Guided Sentinel Lymph Node Mapping in 110 Nonsmall Cell Lung Cancer Patients

Sentinel lymph node identification has been tested in lung cancer patients with conflicting results. The present study was designed to assess the sensitivity, negative predictive value, and accuracy of intraoperative sentinel lymph node mapping by means of a radio-guided method in patients with nonsmall cell lung cancer to find the most appropriate definition of sentinel lymph node and to evaluate the usefulness of different particle sizes of radiocolloid. One hundred ten patients with clinically N0 nonsmall cell lung cancer were enrolled in the pilot study of intraoperative sentinel node identification. Four quadrants of the peritumoral tissue were injected with 2 mL of 0.5 mCi technetium-99m suspension. Four radiocolloids of different particle size were used. After complete lymphadenectomy, all resected lymph nodes were examined with hematoxylin-eosin staining. All sentinel nodes negative for metastases by routine staining were searched further for metastatic deposits with both serial sections and immunohistochemistry for cytokeratins. The radio-guided method had a high identification rate, a high sensitivity, and a high negative predictive value (100%, 87%, and 93%, respectively) when immunohistochemistry was considered. When standard hematoxylin and eosin staining was applied, sensitivity and negative predictive value of sentinel lymph node labeling was lower (74% and 89%, respectively). No significant differences were found in either the sensitivity or negative predictive value among the colloid solutions of different particle size used in radio labeling, although smaller particles have shown a tendency to produce better results. The radio-guided technique provides efficient sentinel lymph node identification in lung cancer. Further studies are warranted to confirm the clinical utility of this strategy.

Lessons learned from two decades of sentinel node biopsies for melanoma

8055 Background: The long term prognosis for patients with melanoma staged by sentinel node biopsy (SNB) remains unclear, largely due to limited follow-up from a variety of small single institution studies. We evaluated our extensive 20-year experience to evaluate the long term prognostic significance of SNB. Methods: We retrospectively reviewed the records of 2001 successive patients who underwent LM/SNB at our center from 1985 until 2004. After preoperative lymphoscintigraphy, blue dye and a hand-held gamma probe were used for intraoperative identification of sentinel nodes (SN). SN were evaluated for metastases by hemotoxylin and eosin and immunohistochemical staining with HMB45, S-100, and more recently with antibodies to melanA. Patients with tumor-positive SN underwent completion dissection (SCLND). Clinicopathological features of the patients, primaries and SN status were evaluated for their influence on survival using multivariate Cox regression analysis. Results: After median follow-up of 49 months (range 1–237). Median age for our patients was 51 years (range 10–91). Of the 2,001 patients, 1584 (79%) had tumor-negative and 417 (21%) had tumor-positive SN. Survival rates were higher in patients with tumor-negative vs. tumor-positive SN (91 + 2% vs. 72 + 5% at 5 years, log-rank p&lt;0.0001; and 84 + 3% vs. 64 + 7% at 10 years, log-rank p&lt;0.0001). Of the 417 patients with SN metastases, 293 (70%) had a single tumor-positive node, 101 (24%) had 2–3 positive nodes, and 25 (6%) had at least 4 positive nodes (sentinel plus nonsentinel). Overall survival was significantly better when metastases were confined to single vs. multiple nodes (77 + 3% vs. 63 + 5%; p=0.0017). Multivariate analysis with Cox regression identified SN status (p&lt;0.0001) as the most important prognostic factor, Hazard Ratio 3.44 (2.47–4.79). Breslow thickness (p&lt;0.0001) and ulceration (p=0.0001) are also independently significant for survival. Gender and primary site were not significant. Conclusions: Our results demonstrate the long term prognostic significance of SN status. LM/SNB should become standard of care for primary melanoma because it is the most accurate factor for the quantification of the risk for recurrence and death available. No significant financial relationships to disclose.

An intraoperative sentinel lymph node identification in breast cancer patients guided by near-infrared fluorescence imaging: Preliminary results

10776 Background: Recently, radioactive tracer, a vital dye, or a combination of both has been applied to detect intraoperative sentinel lymph nodes (SLN) in early breast cancers. In this study, we present a novel method in SLN identification that provides with high detection and low false-negative rates. Methods: This study enrolled 19 patients with a tumor less than 3 cm in diameter. Their mean age was 49.6 years. Preoperative TNM stage was I in 13 cases, IIa in 4, and IIb in 2, respectively. Initially the combination dye of indocyanine green and indigocarmine was injected subdermally in the areolar. Fluorescence imaging (photodynamic eye: Hamamatsu Photonics Co.) was obtained using a charge coupled device camera with a cut filter as the detector, and light emitting diodes at 760 nm as the light source. Subcutaneous lymphatic channels draining from the areola to the axilla or other directions were visible by fluorescence imagings immediately. After incising the axillary skin on the disappeared point of fluorescence image, SLN was then dissected under the guidance of fluorescence. Results: In all patient, lymphatic channels and SLN were successfully visualized. SLN was observed before skin incision in two patients. The number of fluorescence SLN ranged from 2 to 11 (mean: 5.5) and blue dyed SLN ranged from o to 6 (mean: 2.3). In the latter, SLN was not identified in one patient. Six patients had lymph node metastases pathologically. All of them were recognized by fluorescence imagings, however, in two patients LN with metastasis were not identified by a vital dye. There were no intra- or postoperative complications associated with SLN identification. Conclusions: This method is feasible and safe to detect SLN intraoperatively with less invasive, real-time observation and no requirement of training. We hope that this method will provide with high detection and low false-negative rates in SLN navigation surgery. No significant financial relationships to disclose.

Use of Lymphoscintigraphy Defines Lymphatic Drainage Patterns Before Sentinel Lymph Node Biopsy for Breast Cancer

Lymphoscintigraphy (LSG) can identify lymphatic drainage patterns before sentinel lymph node (SLN) biopsy is performed in patients with early-stage breast cancer, but the importance of extraaxillary SLNs seen on LSG is unknown. We assessed whether drainage patterns seen on LSG were associated with histologic findings in axillary SLNs recovered at SLN biopsy. From a prospectively maintained database, we identified 1,201 clinically node-negative patients with invasive breast cancer who underwent preoperative LSG and axillary SLN biopsy. Patient and tumor characteristics, LSG results, and final SLN pathology results were examined. LSG showed drainage to internal mammary (IM) nodes in 1.6% of patients, axillary nodes in 68.1%, both IM and axillary nodes in 19.8%, and no drainage in 10.3%. Drainage to IM nodes was observed for tumors in all quadrants of the breast. Patients with IM drainage had a younger median age than patients without IM drainage (51.8 versus 58.3 years, respectively; p < 0.001). The intraoperative axillary SLN identification rate was higher when axillary drainage was observed on LSG than when it was not observed (98.7% versus 93.0%, respectively; p < 0.001), but the LSG drainage pattern was not associated with pathologic status of the SLN or number of metastatic SLNs. At a median followup of 32 months, 4 patients had regional nodal recurrence. Almost one-fourth of patients had lymphatic drainage to the extraaxillary lymph nodes, particularly the IM nodes, seen on LSG. Extraaxillary drainage seen on LSG did not preclude identification of axillary SLNs at operation. Longterm followup of patients with lymphoscintigraphic evidence of extraaxillary drainage is needed to determine whether regional and systemic recurrence patterns differ in these patients.

Lymphoscintigraphy Does Not Enhance Sentinel Node Identification or Alter Management of Patients With Early Breast Cancer

Lymphoscintigraphy (LS) is often performed before sentinel lymph node dissection (SLND) for breast cancer. The purpose of this study was to determine whether routine LS enhances rate of identification of sentinel nodes (SN), and if findings on LS alter either the SLND procedure or the subsequent patient management. LS using technetium-99m sulfur colloid (99mTc) was performed in 136 consecutive patients undergoing SLND for invasive breast cancer. Three equal aliquots of 99mTc were injected peritumorally, and LS images were obtained at 60 to 120 min after 99mTc injection. Data were collected on the success of LS to visualize SN. Information regarding body mass index (BMI), biopsy type (core vs excisional), tumor location (medial vs lateral), and SN positivity were recorded and comparison was made with success of operative SN identification. In all SLND cases, 1% lymphazurin blue dye was used in addition to the 99mTc. LS failed to identify an SN in 9 of 136 cases (6.6%). Failed mappings did not correlate with biopsy type, tumor location, or SN positivity. There was a positive correlation between increased BMI and failed LS (p = <0.001). Failed LS did not predict operative SLND failure, as an SN was identified in 100% of cases (136/136), including the 9 with a failed LS. In 67% (6/9) of the failed LS, the SN was both hot and blue at operation. Internal mammary (IM) drainage was observed in 4% (6/136) of LS. Positive SN were found in 26% (35/136) of patients. Findings on LS did not affect adjuvant treatment decisions in any patient. There was a correlation between failed LS and BMI, but no correlation with biopsy type or tumor location. Drainage to extraaxillary sites was rare. LS findings did not enhance success of intraoperative identification of SN or alter the postoperative management of patients with early stage breast cancer.

Blue-dye intraoperative sentinel lymph node mapping in early non-small cell lung cancer

Aims The blue-dye staining method of sentinel lymph node identification in lung cancer patients has been scarcely reported. The study was designed to assess the sensitivity, accuracy and negative predictive value (NPV) of intraoperative sentinel lymph node mapping in patients with non-small cell lung cancer by means of staining with colloid or water solution of blue dye. Patients and Methods One hundred and ten patients with clinically confirmed NO non-small cell lung cancer were enrolled into prospective study of intraoperative sentinel node identification. Four quadrants of the peritumoral tissue were injected with 4 ml of blue dye.After complete lymphadenectomy, all resected lymph nodes were examined with conventional hematoxylin-eosine staining. All negative sentinel nodes were searched for metastatic deposits with both serial sections and immunohistochemistry for cytokeratines. Results The blue-dye technique was characterized by unacceptably low sentinel node identification rate (IR) and low sensitivity (27% and 67% respectively). No significant differences were found in either the sensitivity or NPV among the colloid or water solutions of the blue dye applied. Although patent blue (colloid) was superior to water solution of methylene blue in identifying sentinel lymph node (identification rate 36% and 22% respectively) the sensitivity and NPV were lower (63% and 80% for patent blue and 75% and 92% for methylene blue respectively). Conclusion The blue-dye staining method of sentinel node identification in non-small cell lung cancer patients is inadequate and should not be recommended for clinical use.

Total laparoscopic radical trachelectomy with intraoperative sentinel node identification for early cervical stump cancer

A 60-year-old patient had undergone a subtotal hysterectomy through a standard laparotomy approach due to multiple uterine myomas 6 years before. She had a 1-month history of postmenopausal uterine bleeding. An endocervical polyp was found and excised. The histopathologic examination showed a poorly differentiated adenocarcinoma. Magnetic resonance imaging of the abdomen and pelvis revealed the mass (4 × 2 × 2.5 cm) without parametrial involvement previously identified on vaginal examination. There was no retroperitoneal adenopathy. The patient was successfully treated with total laparoscopic radical trachelectomy in association with laparoscopic intraoperative detection of the sentinel lymph node.

Intraoperative Detektion von Sentinel‐Lymphknoten beim malignen Melanom der Haut‐Vitalfärbung allein versus Vitalfärbung plus Gammasonde

Zusammenfassung Hintergrund: Im Vergleich zur alleinigen Vitalfärbung der Lymphabflusswege bei der Sentinel‐Lymphknotendissektion hat die intraoperative Anwendung einer Gamma‐Detektionssonde die Identifikationsraten verbessert. In der vorliegenden retrospektiven Studie wird der Einfluss der Gamma‐Detektion hinsichtlich weiterer Aspekte ausführlich analysiert. Patienten und Methodik: 81 Patienten, bei denen zur intraoperativen Detektion des Sentinel‐Lymphknotens (SLK) ausschließlich Patentblau zum Einsatz kam, wurden mit 247 Patienten verglichen, bei denen zusätzlich eine Gamma‐Sonde verwendet wurde. Ergebnisse: Die Einführung der Gamma‐Sonde erbrachte eine Steigerung der SLK‐Detektionsrate von 87,7 % auf 99,2 % (P &lt; 0,00001). Die Zahl der exzidierten SLK erhöhte sich von 1,4 ± 0,9 auf 1,8 ± 0,09 (P &lt; 0,00001). Die „klinische Falsch‐negativ‐Rate” sank von 15,8 % auf 9,6 %. Die Positivitätsrate der komplettierenden Lymphknotendissektion sank von 50 % auf 26,6 %. Die Gamma‐Sonden‐gesteuerte Präparation hatte weniger Serome zur Folge (5,1 % versus 15 %, P = 0,01). Die Überlebens‐ und Rezidivraten nach alleiniger Vitalfärbung bzw. zusätzlicher Gamma‐Detektion unterschieden sich nicht signifikant. Die Wahrscheinlichkeit, innerhalb von 5 Jahren ein Rezidiv im Lymphknotengebiet zu entwickeln war 7,9 % nach negativer SLK‐Dissektion und 25,3 % nach positiver SLK‐Dissektion mit anschließender komplettierender Lymphknotendissektion. Schlussfolgerungen: Der kombinierte Einsatz von Vitalfärbung und Gamma‐Sonde erhöhte die Sensitivität und senkte das Risiko der postoperativen Seromentwicklung, war aber ohne signifikanten Einfluss auf die Rezidiv‐ und Überlebensraten.

Total laparoscopic radical hysterectomy with intraoperative sentinel node identification in patients with early invasive cervical cancer

Objectives To describe the feasibility and results of total laparoscopic radical hysterectomy with intraoperative sentinel lymph node identification in patients with early cervical cancer. Methods Between March 2001 and October 2003, 12 patients with FIGO stage IA 2 ( n = 1) or IB 1 ( n = 11) cancer of the cervix underwent surgical treatment through the laparoscopic route. All patients underwent a laparoscopic sentinel node identification with preoperative lymphoscintigraphy (technetium-99 m colloid albumin injection around the tumor) and intraoperative lymphatic mapping with isosulfan blue dye and a laparoscopic gamma probe followed by systematic bilateral pelvic lymphadenectomy and laparoscopic type II ( n = 5) or type III ( n = 7) hysterectomy. Results A mean of 2.5 sentinel nodes per patient (range 1−4) was detected, with a mean of 2.33 nodes per patient by gamma probe and a mean of 2 per patient after blue injection (combined detection rate 100%). The most frequent localization of the nodes was the interiliac region. Histopathologic examination of sentinel nodes including cytokeratin immunohistochemical analysis did not show metastasis. Microscopic nodal metastases were not found. The mean number of resected pelvic nodes was 18.6 per patient (range 10–28). The operation was performed entirely by laparoscopy in all patients and no case of laparotomy conversion was recorded. The mean duration of operation was 271 min (range 235–300), with a mean blood loss of 445 mL (range 240–800), and a mean length of stay of 5.25 days (range 3−10). No major intraoperative complications occurred. After a median follow-up of 20 months (range 5–34), all patients are free of disease. Conclusions This study shows the feasibility of the combination of laparoscopic intraoperative sentinel node mapping and laparoscopic radical surgery in the context of minimally invasive surgery for the management of patients with early cervical cancer.

Incidence of nonlocalization of sentinel lymph nodes using preoperative lymphoscintigraphy in 74 consecutive head and neck melanoma and Merkel cell carcinoma patients.

Lymphatic drainage pathways in the head and neck region are more variable than in any other location of the body. Occasionally, head and neck lymphoscintograms fail to identify a definitive lymphatic drainage pattern, making preoperative and intraoperative identification of sentinel nodes very difficult. The purpose of this study was to determine the incidence of nonlocalization on lymphoscintigraphy of sentinel nodes in patients with head and neck cutaneous malignancies. A retrospective chart review was conducted of a single surgeon's (WKS) 135 consecutive head and neck melanoma and Merkel cell cancer patients from August 1997 to August 2002. In all cases. technetium-99m sulfur colloid was the radioactive tracer used by the nuclear medicine department to perform the lymphoscintograms. Of the 135 patients, 74 underwent preoperative lymphoscintigraphy in preparation for performing a sentinel lymph node biopsy. Of these 74 patients, 5 (6.8%) were found to have nonlocalization of a sentinel node(s). Of the 5 patients who failed to localize, 3 had primary lesions near the midline scalp, while 2 had primary lesions located on the cheek. Two of the 5 patients underwent reinjection of the radioisotope by the treating surgeon (WKS) but failed to further localize the radiotracer. All 5 patients went on to have wide local excision of the primary cancer on the day of the lymphoscintogram, as well as undergoing intraoperative examination of all head and neck nodal basins with a handheld gamma detector. No focal areas of radiation were identified and no lymph nodes were biopsied. To date, 1 patient has developed distant metastases and has succumbed to her disease. The remaining 4 patients are free of disease. In a series of 135 consecutive patients with head and neck cutaneous malignancies, 74 of whom were treated with preoperative lymphoscintograms, a nonlocalization rate of 6.8% was found. This is a significant rate of nonlocalization and reflects either the inherent difficulty in imaging the head and neck region and/or the possible rapid rate of dye washout via multiple lymphatic drainage pathways that exist in this location.

In vivo identification of sentinel lymph nodes for clinical stage I non-small cell lung cancer for abbreviation of mediastinal lymph node dissection

Background: We previously reported that an identification of sentinel lymph node (SN) with a techenetium-99m ( 99 m Tc ) tin colloid by ex vivo counting, i.e. the radio-activity of dissected lymph nodes, was a reliable method of establishing the first site of nodal metastasis in non-small cell lung cancer [J. Thorac. Cardiovasc. Surg. 124(2002)486]. However, for SN navigation surgery, SN should be identified before lymph node dissection (in vivo) but not after that (ex vivo). In order to reduce mediastinal lymph node dissection for clinical stage I non-small cell lung cancer (NSCLC) by SN navigation surgery, the SN identifications for hilar lymph nodes by ex vivo counting, and for mediastinal lymph nodes by in vivo, were evaluated. Methods: Intra-operative SN identification using 99 m Tc tin colloid was conducted on 104 patients with clinical stage I NSCLC who had had major lung resections with mediastinal lymph node dissections. The hilar SNs were identified by ex vivo counting (after lung resection) and the mediastinal SNs were identified by in vivo counting (before lymph node dissection). To evaluate the accuracy of mediastinal SN identification by in vivo counting, it was compared with the data by ex vivo counting. Results: SNs were identified in 84 patients (81%). SNs were identified at the hilum by ex vivo counting in 78 patients (93%) and at the mediastinum by in vivo counting in 40 patients (48%). While 15 patients had lymph node metastases, i.e. N1 in six and N2 in nine, the SNs could be found to have metastases during operation in 13 of the 15 patients (87%). The in vivo counting of the mediastinum missed out the mediastinal SNs identified by ex vivo counting in four of the 84 patients (5%). Conclusion: If the hilar SNs identified by ex vivo counting and the mediastinal SNs identified by in vivo counting had no metastases, then mediastinal lymph node dissection could be abbreviated for patients with clinical stage I NSCLC.

Usefulness of a solid-state gamma camera for sentinel node identification in patients with breast cancer

A solid-state gamma camera was recently developed. This tool may enable intra-operative imaging of sentinel nodes in breast cancer. The aim of the present study was to evaluate the usefulness of a solid-state gamma camera for the pre- and intra-operative identification of sentinel nodes in patients with breast cancer. Breast cancer patients with clinically negative nodes underwent sentinel node biopsy using dye and radioisotopes. Lymphoscintigraphy using both the conventional Anger camera and the solid-state gamma camera was performed the day before surgery. Sentinel nodes were intra-operatively identified using the gamma probe and imaged with a solid-state gamma camera, and then excised. When several sentinel nodes were present, these steps were repeated. Twenty-nine patients (30 basins) were enrolled in the study. The mean patient age was 54 years and the mean tumor size was 16 mm. A total of 41 sentinel nodes were identified using the Anger camera or the solid-state gamma camera pre-operatively. Thirty-eight sentinel nodes (92.7%) were identified using both the Anger camera and the solid-state gamma camera, 1 sentinel node (2.4%) was identified using the Anger camera alone, and 2 sentinel nodes (4.9%) were identified using the solid-state gamma camera alone. A total of 63 sentinel nodes were identified using the gamma probe or the solid-state gamma camera intra-operatively, and were excised. Fifty-seven sentinel nodes (90.5%) were identified using both the gamma probe and the solid-state gamma camera, 3 sentinel nodes (4.8%) were identified using the gamma probe alone, and 3 sentinel nodes (4.8%) were identified using the solid-state gamma camera alone. The solid-state gamma camera is useful for pre- and intra-operative identification of sentinel nodes in breast cancer. The significance of the solid-state gamma camera could be that it compensates for the gamma probe when the gamma probe cannot identify some sentinel nodes because of the shine through effect, and avoids leaving the residual sentinel nodes behind the axilla intra-operatively.

Intraoperative sentinel node identification with Technetium-99m-labeled nanocolloid in patients with cancer of the uterine cervix: A feasibility study

The objective of this study is to determine the feasibility of intraoperative lymphatic mapping in patients with cervical carcinoma. Patients with early-stage cervical cancer, scheduled to undergo a Wertheims radical hysterectomy and pelvic lymphadenectomy, were eligible for the study. Technetium-99-m-labeled nanocolloid was injected intracervically at two locations around the tumor 3–6 hours before the operation. Images were recorded immediately and 2.5 hours later using a gamma camera. During the operation sentinel nodes (SLN) were identified using a handheld or laparoscopic gamma-detection probe (Navigator, Auto-Suture). After resection of the SLNs a standard pelvic (and para-aortic) lymphadenectomy was performed. The results of the histopathology of SLNs and non-SLNs were compared. The procedure was well tolerated by 24 of 25 patients. One or more SLN could be identified in 21 out of 25 patients. In one patient who was preoperatively irradiated, in two patients who had had a cone biopsy, and in one patient without previous interventions, no SLN could be detected. The mean time for identification was 5 minutes. In 16 patients, pathologic examination showed no metastatic disease in both SLNs and non-SLNs, whereas metastases were found in the SLN in five patients (in one case only SLN involved, four cases SLN and respectively 3, 11, 22 and 31 other positive nodes). This study shows that identification of SLNs in cancer of the uterine cervix is feasible with preoperatively administered 99mTc-labeled nanocolloid. To date, no false negative SLNs have been found, but expansion of the study is necessary to determine possible clinical application of this new technique.

Kit Formulation for the Preparation of Radioactive Blue Liposomes for Sentinel Node Lymphoscintigraphy

A radioactively labeled blue liposome formulation was developed for use in presurgical lymphoscintigraphy and intraoperative sentinel node localization to avoid the differing injection site clearance kinetics of the conjunctive use of separate formulations of low molecular weight blue dye and radioactively labeled macromolecular sulfur colloid. Blue liposomes containing glutathione in the internal aqueous phase were prepared from blue dyed lipids obtained by covalently binding Reactive Blue II to phosphatidylethanolamine (PE) fractions of phospholipid extracts. Four phospholipid extracts with differing PE fractions and a centrifugation technique were evaluated with the goal of maximizing the blue color intensity of the formulation. Stability of the formulations was evaluated by studying radiolabeling efficiency (using a membrane permeable lipophilic carrier of the commonly used diagnostic radionuclide, technetium-99m) and particle-size distribution over 30-60-day periods. Blue color was not altered by varying the PE content, while centrifugation was an effective and convenient method to maximize the blue color intensity of the final preparation. The particle size distribution of the prepared liposomes ranged from 200-300 nm (considered ideal for lymphoscintigraphy studies) and did not change significantly, while radiolabeling efficiency exceeded 80% for up to 1 month. The described kit formulation for the preparation of radiolabeled blue liposomes is suitable for commercial production allowing widespread clinical use. The combination of a means of visual identification and tracking of the liposomes through the lymphatic channels along with the ability to trace the preparation using standard radiation detection instrumentation provides the surgeon with an improved radiolabeled compound for lymphoscintigraphy and intraoperative sentinel lymph node identification.