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This study aimed to assess the value of dual-timepoint 18 F-FDG PET/CT in the prediction of lymph node (LN) status in patients with invasive vulvar cancer (VC) scheduled for inguinofemoral LN dissection. Methods: From April 2013 to July 2015, all consecutive patients with VC scheduled for inguinofemoral LN dissection were prospectively enrolled. All patients underwent a preoperative whole-body 18 F-FDG PET/CT scan at 1 h (standard examination) and an additional scan from T11 to the groins at 3 h (delayed examination) after 18 F-FDG injection. On both scans, each groin was visually scored 0 or 1 concerning 18 F-FDG LN uptake relative to background. Semiquantitative analysis included SUV max and the corresponding retention index of SUV max , measured on both scans. The optimal cutoff value of these parameters was defined using a receiver-operating-characteristic analysis. Histopathology was the standard of reference. Results: Thirty-three patients were included, with a total of 57 groins dissected and histologically evaluated. At histopathology, 21 of 57 (37%) groins contained metastatic LNs. Concerning visual score, sensitivity, specificity, negative predictive value, positive predictive value, and accuracy were 95.2%, 75%, 96.4%, 69%, and 82.5% on standard scanning and 95.2%, 77.8%, 96.6%, 71.4%, and 84.2% on delayed scanning, respectively. At receiver-operating-characteristic analysis, sensitivity and specificity were 95.2% and 77.8% on standard and delayed 18 F-FDG PET/CT for an SUV max cutoff of greater than 1.32 and 1.88, respectively, and 95.2% and 80% for a retention index of SUV max cutoff of greater than 0. Conclusion: Standard 18 F-FDG PET/CT is an effective preoperative imaging method for the prediction of LN status in VC, allowing the prediction of pathologically negative groins and thus the selection of patients suitable for minimally invasive surgery. Delayed 18 F-FDG PET/CT did not improve the specificity and the positive predictive value in our series. Larger studies are needed for a further validation., (© 2017 by the Society of Nuclear Medicine and Molecular Imaging.)

Purpose: To determine the lymphatic drainage pattern using SPECT/CT in clinically node-negative (cN0) patients with vulvar cancer, and to evaluate the possible implications for the extent of inguinal lymph node dissection., Methods: A total of 83 patients with vulvar cancer scheduled for sentinel node (SN) biopsy were injected peritumorally with radioactive nanocolloid particles followed by lymphoscintigraphy and SPECT/CT for anatomical localization. The SN and higher-echelon nodes on SPECT/CT were located in different zones in the groin and pelvic region. The groin was divided into five zones according to Daseler et al.: four zones obtained by drawing two perpendicular lines over the saphenofemoral junction and one zone directly overlying this junction. The nodes in the pelvic region were classified into three zones: external iliac/obturator, the common iliac and the paraaortic zones., Results: A total of 217 SNs and 202 higher-echelon nodes were localized on SPECT/CT. All SNs were located in the five zones according to Daseler et al.: 149 (69%) in the medial superior region, 31 (14%) in the medial inferior region, 22 (10%) in the central region, 14 (6.5%) in the lateral superior region and only 1 (0.5%) in the lateral inferior region. The higher-echelon nodes were located both in the groin (15%) and in the pelvic region (85%)., Conclusion: In patients with cN0 vulvar cancer, lymphatic drainage occurs predominantly to the medial regions of the groin. Drainage to the lateral inferior region of the groin is only incidental and in SN-positive patients this zone might be spared in subsequent extended lymph node dissection. This may lead to a decrease in the morbidity associated with this procedure. SPECT/CT is able to personalize lymphatic mapping, providing detailed information about the number and anatomical location of SNs for adequate surgical planning in the groin.

Purpose: In the present study we describe patients with non-palpable breast lesions, in which an Iodine-125 ((125)I)-marker (or "seed") for excision of the primary tumour and Technetium-99m nanocolloid ((99m)Tc-nanocolloid) for sentinel node biopsy (SNB) are used simultaneously. The purpose was to investigate any interference between (125)I-seeds and (99m)Tc-nanocolloid by an in vitro and in vivo analysis., Methods: Contrast/interference-ratios between (125)I and (99m)Tc count-rates were determined in vitro using a realistic simulation model. Measurements were performed with 3 gamma-probes with different crystal materials. In 25 consecutive patients (99m)Tc-nanocolloid was intratumourally administered at the site of a previously implanted (125)I-seed. Respectively, the (125)I-setting and (99m)Tc-setting of the gamma-probe guided the wide local excision and SNB and maximum counts-per-second (cps) were measured., Results: In vitro the different probes varied in (125)I- and (99m)Tc-sensitivity. The contrast-ratio between (125)I and (99m)Tc in the (125)I-channel was 4.6 for a 3-month-old (125)I-seed using the most appropriate gamma-probe. In vivo the gamma-probe in the (125)I-setting measured a median of 16,300 cps at the tumour site compared to 4820 cps using the (99m)Tc-setting. The (125)I-seed could be well distinguished from the (99m)Tc-nanocolloid in 92% of the patients and 96% required a single operation. The SNB was successful in all patients., Conclusions: Simultaneous use of (125)I-seeds and (99m)Tc-nanocolloid is possible under well-standardised conditions. Non-palpable breast lesions can be safely excised using the (125)I-seed in combination with a SN procedure. Use of (125)I-seeds is a next step within fine-tuning breast-conserving surgery that should lead to further investigation to confirm its value., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Conventional sentinel node (SN) mapping is performed by injection of a radiocolloid followed by lymphoscintigraphy to identify the number and location of the primary tumor draining lymph node(s), the so-called SN(s). Over the last decade research has focused on the introduction of new imaging agents that can further aid (surgical) SN identification. Different tracers for SN mapping, with varying sizes and isotopes have been reported, most of which have proven their value in a clinical setting. A major challenge lies in transferring this diagnostic information obtained at the nuclear medicine department to the operating theatre thereby providing the surgeon with (image) guidance. Conventionally, an intraoperative injection of vital blue dye or a fluorescence dye is given to allow intraoperative optical SN identification. However, for some indications, the radiotracer-based approach remains crucial. More recently, hybrid tracers, that contain both a radioactive and fluorescent label, were introduced to allow for direct integration of pre- and intraoperative guidance technologies. Their potential is especially high when they are used in combination with new surgical imaging modalities and navigation tools. Next to a description of the known tracers for SN mapping, this review discusses the application of hybrid tracers during SN biopsy and how the introduction of these new techniques can further aid in translation of nuclear medicine information into the operating theatre.

Beside the classical applications of sentinel lymph node mapping, some new procedures are emerging and showing feasibility and clinical utility. In this chapter, we will report on sentinel lymph node mapping in 1) malignancies of the female reproductive system (cervical cancer, endometrial cancer, vulvar cancer and ovarian cancer); 2) malignancies of the male reproductive system (prostate cancer, penile cancer and testicular cancer); 3) malignancies in kidney and bladder. This paper presents the uncommon applications of sentinel lymph node mapping in urogenital neoplasms.

Radioguided surgery has been investigated and applied to almost any neoplastic disease that is surgically treated. The impact of radioguided surgery on the surgical management of cancer patients includes relevant and real-time information to the surgeon regarding the location and extent of the disease, as well as regarding the assessment of surgical resection margins. Despite the fact that sentinel lymph node biopsy has been worldwide accepted as a highly accurate staging method for various solid cancers (among which breast cancer and cutaneous melanoma), some potential intraoperative drawbacks still remain. This article provides an update on currently available perioperative techniques regarding the use of radiotracers for radioguided surgery and sentinel lymph node mapping and biopsy, in particular in combination with vital dyes or other agents. The integration of computer technology and data processing makes it possible to integrate anatomic and functional images together with 3D rendering systems. This facilitates the targeted-tissue perioperative localization, especially in anatomically complex areas. Furthermore, we provide an update on advances in the integration of intraoperative imaging devices as well as optical tracers for the surgical management of patients. Evidence is emerging that these devices, together with new potential tracers, may improve intraoperative identification of sentinel nodes and/or tumors. A detailed presentation on a portable gamma camera in breast cancer patients, and the application of perioperative imaging devices in gynaecological cancers are included. Other important procedures, such as ROLL and RSL for occult lesion excision in the breast and other organs, are extensively discussed.

A few years ago SPECT/CT was successfully incorporated into the sentinel node (SN) procedure for breast cancer and melanoma. Important contributions of SPECT/CT in these two malignancies were the anatomical localization of SNs already visualized on planar images, the detection of additional SNs in aberrant basins, and the depiction of SNs in cases with no visualization on planar images. Recently, in a large series of melanoma patients the use of SPECT/CT was associated with the detection of more metastatic SNs and a higher rate of disease-free survival. Following the experiences in breast cancer and melanoma, SPECT/CT has been applied in oral cavity cancer as well as in urological and gynaecological malignancies. In the areas of lymphatic drainage of these malignancies (head and neck, pelvis, and upper abdomen) SPECT/CT appears to be essential to localize SNs, providing surgeons with helpful anatomical landmarks to plan SN biopsies. In gastrointestinal and lung malignancies SPECT/CT has only incidentally been used. With the improvement of the CT component in the second generation of SPECT/CT gamma cameras, nuclear physicians today can identify lymph nodes corresponding with the radioactive SNs. This is possible using a display of SPECT/CT similar to that of conventional tomography. Multiplanar reconstruction enables to correlate radioactive sentinel nodes seen on fused SPECT/CT with lymph nodes seen on CT, and the use of cross-reference lines allows the navigation between axial, coronal and sagittal views. This visual information is helpful for the intraoperative procedure and for post-excision assessment using portable devices. Fused SPECT/CT images may also be three-dimensionally displayed, improving anatomical SN localisation and recognition. This recent imaging improvement is leading to a new paradigm of "see and open" in contraposition to the former "open and see" in the SN procedure. The new mixed reality protocols which are able to transfer SPECT/CT to the operating room for surgical navigation will reinforce this "see and open" concept. However, a comprehensive interpretation of SPECT/CT together with lymphoscintigraphy is necessary to identify radioactive lymph nodes as sentinel nodes and classify them into different categories that are important for the intraoperative procedure.

Purpose: The management of regional nodes of penile squamous cell carcinoma has changed with time due to improved knowledge about diagnosis and treatment. To determine whether changes in the treatment of regional nodes have improved survival, we compared contemporary 5-year cancer specific survival of patients with squamous cell carcinoma of the penis with that of patients in previous cohorts., Materials and Methods: In an observational cohort study of 1,000 patients treated during 56 years 944 were eligible for analysis. Tumors were staged according to the 2009 TNM classification, and patients were divided into 4 cohorts of 1956 to 1987, 1988 to 1993, 1994 to 2000 and 2001 to 2012, reflecting changes in clinical practice regarding regional nodes. Kaplan-Meier survival curves with the log rank test and Cox proportional hazards modeling were used to examine trends in 5-year cancer specific survival., Results: The 5-year cancer specific survival of patients with cN0 disease treated between 2001 and 2012 was 92% compared to 89% (1994 to 2000), 78% (1988 to 1993) and 85% (1956 to 1987). The 5-year cancer specific survival improved significantly since 1994, the year dynamic sentinel node biopsy was introduced, at 91% (1994 to 2012) vs 82% (1956 to 1993) (p = 0.021). This conclusion still holds after adjustment for pathological T stage and grade of differentiation (HR 2.46, p = 0.01). Extranodal extension, number of tumor positive nodes and pelvic involvement in node positive (pN+) cases were associated with worse 5-year cancer specific survival., Conclusions: Despite less surgery being performed on regional nodes, 5-year cancer specific survival has improved in patients with cN0 disease. The number of tumor positive nodes, extranodal extension and pelvic involvement were highly associated with worse cancer specific survival in patients with pN+ disease. In this group other treatment strategies are needed as no improvement was observed., (Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: To investigate the value of response monitoring in both the primary tumour and axillary nodes on sequential PET/CT scans during neoadjuvant chemotherapy (NAC) for predicting complete pathological response (pCR), taking the breast cancer subtype into account., Methods: In 107 consecutive patients 290 PET/CT scans were performed at baseline (PET/CT1, 107 patients), after 2 - 3 weeks of chemotherapy (PET/CT2, 85 patients), and after 6 - 8 weeks (PET/CT3, 98 patients). The relative changes in SUVmax (from baseline) of the tumour and the lymph nodes and in both combined (after logistic regression), and the changes in the highest SUVmax between scans (either tumour or lymph node) were determined and their associations with pCR of the tumour and lymph nodes after completion of NAC were assessed using receiver operating characteristic (ROC) analysis., Results: A pCR was seen in 17 HER2-positive tumours (65 %), 1 ER-positive/HER2-negative tumour (2 %), and 16 triple-negative tumours (52 %). The areas under the ROC curves (ROC-AUC) for the prediction of pCR in HER2-positive tumours after 3 weeks were 0.61 for the relative change in tumours, 0.67 for the combined change in tumour and nodes, and 0.72 for the changes in the highest SUVmax between scans. After 8 weeks equivalent values were 0.59, 0.42 and 0.64, respectively. In triple-negative tumours the ROC-AUCs were 0.76, 0.84 and 0.76 after 2 weeks, and 0.87, 0.93 and 0.88 after 6 weeks, respectively., Conclusion: In triple-negative tumours a PET/CT scan after 6 weeks (three cycles) appears to be optimally predictive of pCR. In HER2-positive tumours neither a PET/CT scan after 3 weeks nor after 8 weeks seems to be useful. The changes in SUVmax of both the tumour and axillary nodes combined correlates best with pCR.

Introduction: Conventional sentinel node (SN) mapping is performed by injecting a radiocolloid followed by lymphoscintigraphy (and SPECT/CT imaging). An extra intraoperative injection with blue dye can then allow for optical identification of the SN. In order to improve the current clinical standard, the hybrid tracer indocyanine green (ICG)-(99m)Tc-nanocolloid was introduced, a tracer that is both radioactive and fluorescent. This feasibility study aimed to evaluate the value of a multimodal-based SN biopsy in vulvar cancer., Materials and Methods: Fifteen patients with vulvar cancer (29 groins) scheduled for SN biopsy were peritumorally injected with ICG-(99m)Tc-nanocolloid followed by lymphoscintigraphy and SPECT/CT imaging to identify the SNs. In thirteen patients, shortly before the start of the operation, blue dye was intradermally injected around the lesion. SNs were harvested using a combination of radiotracing, fluorescence imaging, and optical blue dye detection. A portable gamma camera was used before and after SN excision to confirm excision of the preoperatively defined SNs., Results: Preoperative lymphoscintigraphy and SPECT/CT imaging visualized drainage to 39 SNs in 28 groins. During the operation, 98% (ex vivo 100%) of the SNs were radioactive. With fluorescence imaging 96% of the SNs (ex vivo 100%) could be visualized. Only 65% of the SNs had stained blue at the time of excision., Conclusion: ICG-(99m)Tc-nanocolloid can be used for preoperative SN identification and enables multimodal (radioactive and fluorescent) surgical guidance in patients with vulvar cancer. The addition of fluorescence-based optical guidance offers more effective SN visualization compared to blue dye., (© 2013.)

Background: If all initially node-positive patients undergo axillary lymph node dissection (ALND) after neoadjuvant chemotherapy (NAC), overtreatment may occur in patients with complete response. Positron emission tomography-computed tomography (PET/CT) during NAC may predict axillary response and select patients appropriate for less invasive treatment after NAC. We evaluated the value of sequential (18)F fluorodeoxyglucose (FDG) PET/CTs during NAC for axillary response monitoring in stage II-III breast cancer., Methods: A total of 219 PET/CTs were performed in 80 patients with cytology-proven, node-positive disease at baseline (PET/CT1, n = 80) and twice during NAC (PET/CT2 n = 62, PET/CT3, n = 77). The relative changes in maximum standardized uptake value (SUVmax) of axillary nodes were examined for their ability to assess pathological response. All patients underwent ALND after chemotherapy, and complete axillary response (pCR), defined as absence of isolated tumor cells and of micro- and macrometastases, served as the reference standard., Results: A total of 32 (40 %) patients experienced axillary pCR. The relative decrease in SUVmax was significantly higher in patients with pCR than in those without, both on PET/CT2 (p < 0.001) and PET/CT3 (p = 0.025). The area under the receiver operating characteristic curve values for PET/CT2 and PET/CT3 were 0.80 (95 % confidence interval 0.68-0.92) and 0.65 (95 % confidence interval 0.52-0.79), respectively. A relative decrease of ≥60 % on PET/CT2 had an excellent specificity (35 of 37, 95 %), a high positive predictive value (12 of 14, 86 %), and a sensitivity of 48 %-that is, it accurately identified histologic pCR in 12 of 25 patients with disease that responded to therapy., Conclusions: (18)F-FDG PET/CT early during NAC is useful for axillary response monitoring in cytology-proven node-positive breast cancer because it identifies pathological response, thus permitting ALND to be spared.

The optimal method for locoregional staging in patients treated with neoadjuvant chemotherapy (NAC), usually ultrasound (US) and pre- or post-chemotherapy sentinel lymph node biopsy (SLNB), remains subject of debate. The aim of this study was to assess the value of 18F-FDG PET/CT for detecting locoregional lymph node metastases in primary breast cancer patients scheduled for NAC. 311 breast cancer patients, scheduled for NAC, underwent PET/CT of the thorax in prone position with hanging breasts. A panel of four experienced reviewers examined PET/CT images, blinded for other diagnostic procedures. FDG uptake in locoregional nodes was determined qualitatively using a 4-point scale (0 = negative, 1 = questionable, 2 = moderately intense, and 3 = very intense). Results were compared with pathology obtained by US-guided fine needle aspiration or SLNB prior to NAC. All FDG-avid extra-axillary nodes were considered metastatic, based on the previously reported high positive predictive value of the technique. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of FDG-avid nodes for the detection of axillary metastases (score 2 or 3) were 82, 92, 98, 53, and 84 %, respectively. Of 28 patients with questionable axillary FDG uptake (score 1), 23 (82 %) were node-positive. Occult lymph node metastases in the internal mammary chain and periclavicular area were detected in 26 (8 %) and 32 (10 %) patients, respectively, resulting in changed regional radiotherapy planning in 50 (16 %) patients. In breast cancer patients scheduled for NAC, PET/CT renders pre-chemotherapy SLNB unnecessary in case of an FDG-avid axillary node, enables axillary response monitoring during or after NAC, and leads to changes in radiotherapy for a substantial number of patients because of detection of occult N3-disease. Based on these results, we recommend a PET/CT as a standard staging procedure in breast cancer patients scheduled for NAC.

Unlabelled: The purpose of this study was to compare the lymphoscintigraphic drainage patterns of a hybrid sentinel node tracer consisting of the fluorescent dye indocyanine green (ICG) and (99m)Tc-nanocolloid with the drainage pattern of (99m)Tc-nanocolloid alone, the current standard tracer in many European countries., Methods: Twenty-five patients with a melanoma in the head and neck region (n = 10), a melanoma on the trunk (n = 6), or penile carcinoma (n = 9) who were scheduled for sentinel node biopsy were prospectively included. First, the standard (99m)Tc-nanocolloid procedure was performed. After injection at the lesion site, lymphoscintigraphy was performed with a 10-min dynamic study and static planar images at 10 min and 2 h after injection, followed by SPECT/CT. The same scintigraphic procedure was repeated after injection of hybrid ICG-(99m)Tc-nanocolloid the same afternoon in 10 patients or the next morning in 15 patients. The paired images of both injections were evaluated, and count rates in the sentinel nodes were calculated and compared. Sentinel nodes were surgically localized using blue dye, a γ-ray detection probe, a portable γ-camera, and a fluorescence camera., Results: Lymphatic drainage was visualized in all 25 patients using (99m)Tc-nanocolloid, leading to the identification of 66 sentinel nodes in total. These same sentinel nodes were also identified during the second scintigraphic procedure with ICG-(99m)Tc-nanocolloid. Moreover, a high correlation between the radioactive counting rates in the sentinel nodes of both scintigraphic studies was observed (mean R(2) = 0.83). Intraoperatively (4-23 h after the second injection), all preoperatively identified sentinel nodes could be localized using radio- and fluorescence guidance combined. In total, 95% of the sentinel nodes could be intraoperatively visualized by means of fluorescence imaging, whereas merely 54% stained blue. Ex vivo, all radioactive sentinel nodes were fluorescent and vice versa. No adverse reactions were observed., Conclusion: The lymphatic drainage pattern of ICG-(99m)Tc-nanocolloid is identical to that of (99m)Tc-nanocolloid. This observation, together with the added value of intraoperative fluorescence guidance, warrants wider evaluation of hybrid ICG-(99m)Tc-nanocolloid as a tracer for sentinel node procedures.

Purpose: To investigate whether lymphoscintigraphy and SPECT/CT after intralesional injection of radiopharmaceutical into each tumour separately in patients with multiple malignancies in one breast yields additional sentinel nodes compared to intralesional injection of the largest tumour only., Methods: Patients were included prospectively at four centres in The Netherlands. Lymphatic flow was studied using planar lymphoscintigraphy and SPECT/CT until 4 h after administration of (99m)Tc-nanocolloid in the largest tumour. Subsequently, the smaller tumour(s) was injected intratumorally followed by the same imaging sequence. Sentinel nodes were intraoperatively localized using a gamma ray detection probe and vital blue dye., Results: Included in the study were 50 patients. Additional lymphatic drainage was depicted after the second and/or third injection in 32 patients (64%). Comparison of planar images and SPECT/CT images after consecutive injections enabled visualization of the number and location of additional sentinel nodes (32 axillary, 11 internal mammary chain, 2 intramammary, and 1 interpectoral. A sentinel node contained metastases in 17 patients (34%). In five patients with a tumour-positive node in the axilla that was visualized after the first injection, an additional involved axillary node was found after the second injection. In two patients, isolated tumour cells were found in sentinel nodes that were only visualized after the second injection, whilst the sentinel nodes identified after the first injection were tumour-negative., Conclusion: Lymphoscintigraphy and SPECT/CT after consecutive intratumoral injections of tracer enable lymphatic mapping of each tumour separately in patients with multiple malignancies within one breast. The high incidence of additional sentinel nodes draining from tumours other than the largest one suggests that separate tumour-related tracer injections may be a more accurate approach to mapping and sampling of sentinel nodes in patients with multicentric or multifocal breast cancer.

Purpose: For oral cavity malignancies, sentinel lymph node (SLN) mapping is performed by injecting a radiocolloid around the primary tumour followed by lymphoscintigraphy. Surgically, SLNs can then be localized using a handheld gamma ray detection probe. The aim of this study was to evaluate the added value of intraoperative fluorescence imaging to the conventional radioguided procedure. For this we used indocyanine green (ICG)-(99m)Tc-nanocolloid, a hybrid tracer that is both radioactive and fluorescent., Methods: Fourteen patients with oral cavity squamous cell carcinoma were peritumourally injected with ICG-(99m)Tc-nanocolloid. SLNs were preoperatively identified with lymphoscintigraphy followed by single photon emission computed tomography (SPECT)/CT for anatomical localization. During surgery, SLNs were detected with a handheld gamma ray detection probe and a handheld near-infrared fluorescence camera. Pre-incision and post-excision imaging with a portable gamma camera was performed to confirm complete removal of all SLNs., Results: SLNs were preoperatively identified using the radioactive signature of ICG-(99m)Tc-nanocolloid. Intraoperatively, 43 SLNs could be localized and excised with combined radio- and fluorescence guidance. Additionally, in four patients, an SLN located close to the primary injection site (in three patients this SLN was located in level I) could only be intraoperatively localized using fluorescence imaging. Pathological analysis of the SLNs revealed a metastasis in one patient., Conclusion: Combined preoperative SLN identification and intraoperative radio- and fluorescence guidance during SLN biopsies for oral cavity cancer proved feasible using ICG-(99m)Tc-nanocolloid. The addition of fluorescence imaging was shown to be of particular value when SLNs were located in close proximity to the primary tumour.

Sentinel node mapping is widely applied in patients with melanoma. Although this type of skin cancer usually drains to the standard regional nodal basins, some patients have drainage to an unpredicted site. Nodes lying along a lymphatic channel, between the primary melanoma site and a common basin, are often called interval, in-transit, ectopic, intercalated, or aberrant nodes. They must be considered sentinel lymph nodes because they receive direct lymphatic drainage from a primary tumor site. Most investigators agree that interval sentinel nodes should be harvested; however, the management of melanoma patients with an involved interval sentinel node without established metastasis in the regional basin downstream is controversial. New and innovating technologies have improved nuclear medicine images, including single-photon emission computed tomography/computed tomography (SPECT/CT), a multimodal technique that fuses the radioactivity distribution detected by SPECT with the anatomic information harvested by CT. SPECT/CT does not replace the conventional planar images; it should be considered as a complementary modality for the search of sentinel lymph nodes. We report three illustrative cases that underline the decisive role of SPECT/CT with two-dimensional and three-dimensional reconstruction images to localize the uncommon periscapular sentinel nodes in patients with melanoma of the posterior trunk. The use of this image fusion technique on these patients leads to improved preoperative visualization of the sentinel nodes, may help identify additional periscapular interval sentinel nodes, and enables precise localization of the nodes with their surrounding anatomic structures. The cases are discussed together with a review of the literature.

Purpose: This study was designed to examine the feasibility of combining lymphoscintigraphy and intraoperative sentinel node identification in patients with head and neck melanoma by using a hybrid protein colloid that is both radioactive and fluorescent., Methods: Eleven patients scheduled for sentinel node biopsy in the head and neck region were studied. Approximately 5 h before surgery, the hybrid nanocolloid labeled with indocyanine green (ICG) and technetium-99m ((99m)Tc) was injected intradermally in four deposits around the scar of the primary melanoma excision. Subsequent lymphoscintigraphy and single photon emission computed tomography with computed tomography (SPECT/CT) were performed to identify the sentinel nodes preoperatively. In the operating room, patent blue dye was injected in 7 of the 11 patients. Intraoperatively, sentinel nodes were acoustically localized with a gamma ray detection probe and visualized by using patent blue dye and/or fluorescence-based tracing with a dedicated near-infrared light camera. A portable gamma camera was used before and after sentinel node excision to confirm excision of all sentinel nodes., Results: A total of 27 sentinel nodes were preoperatively identified on the lymphoscintigraphy and SPECT/CT images. All sentinel nodes could be localized intraoperatively. In the seven patients in whom blue dye was used, 43% of the sentinel nodes stained blue, whereas all were fluorescent. The portable gamma camera identified additional sentinel nodes in two patients. Ex vivo, all radioactive lymph nodes were fluorescent and vice versa, indicating the stability of the hybrid tracer., Conclusions: ICG-(99m)Tc-nanocolloid allows for preoperative sentinel node visualization and concomitant intraoperative radio- and fluorescence guidance to the same sentinel nodes in head and neck melanoma patients.

Background: Integration of molecular imaging and in particular intraoperative image guidance is expected to improve the surgical accuracy of laparoscopic lymph node (LN) dissection., Objective: To show the applicability of combining preoperative, intraoperative, and postoperative sentinel node imaging using an integrated diagnostic approach based on an imaging agent that is both radioactive and fluorescent., Design, Setting, and Participants: Before surgery, multimodal indocyanine green (ICG)-(99m)Tc-NanoColl was injected into the prostate. Subsequent lymphoscintigraphy and single-photon emission computed tomography/computed tomography (SPECT/CT) imaging of pelvic nodes was performed to determine the location of the sentinel lymph nodes (SLNs) preoperatively. During the surgical procedure a fluorescence laparoscope, optimized for detection in the near infrared range, was used to visualize the nodes identified on SPECT/CT. Eleven patients scheduled for robot-assisted laparoscopic prostatectomy (RALP) with an increased risk of nodal metastasis, based on Memorial Sloan-Kettering Cancer Center/Kattan nomogram estimation, participated in a pilot assessment (N09IGF)., Surgical Procedure: Patients underwent RALP with LN dissection for prostate cancer., Measurements: Radioactive and fluorescent signals were monitored using different modalities, and the correlation between the two types of signals was studied. The location of preoperatively detected SLNs was documented., Results and Limitations: Preoperatively, SLNs were identified by SPECT/CT, and the multimodal nature of the imaging agent also enabled intraoperative detection via fluorescence imaging. Fluorescence particularly improved surgical guidance in areas with a high radioactive background signal such as the injection site. Ex vivo analysis revealed a strong correlation between the radioactive and fluorescent content in the excised LNs. Fluorescence detection is limited by the severe tissue attenuation of the signal. Therefore, radio guidance to the areas of interest is still desirable., Conclusions: Initial data indicate that multimodal ICG-(99m)Tc-NanoColloid, in combination with a laparoscopic fluorescence laparoscope, can be used to facilitate and optimize dissection of SLNs during RALP procedures., (Copyright © 2011 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Unlabelled: We introduced and evaluated a portable gamma-camera for intraoperative visualization of sentinel nodes in the head and neck region., Methods: Planar lymphoscintigraphy and SPECT/CT were performed after peritumoral injection of (99m)Tc-nanocolloid in 25 patients (head and neck melanoma or oral cavity carcinoma). Sentinel nodes were localized intraoperatively with a portable gamma-camera and a hand-held gamma-probe. The portable gamma-camera was used to determine the distribution of remaining radioactivity after excision of the sentinel nodes., Results: The portable gamma-camera visualized all 70 preoperatively identified sentinel nodes. Sentinel nodes at difficult sites could be localized more efficiently, and in 6 patients, 9 additional nodes (1 tumor-positive) were identified with the portable gamma-camera after excision., Conclusion: Intraoperative identification of sentinel nodes in the head and neck region with a portable gamma-camera is feasible and might lead to detection of more sentinel nodes.

Unlabelled: Paraaortic sentinel node biopsy may be a challenging procedure because the sentinel nodes are located retroperitoneally in close proximity to vital structures. The purpose of this study was to describe and evaluate the value of preoperative SPECT/CT for lymphatic mapping, and a portable gamma-camera for intraoperative radioguidance, in patients with paraaortic sentinel nodes., Methods: We evaluated our practice in 18 patients, who were treated at The Netherlands Cancer Institute with sentinel lymphadenectomy for different urologic malignancies and showed paraaortic drainage on preoperative images. After intratumoral injection of (99m)Tc-nanocolloid, the patients underwent sequential planar lymphoscintigraphy, hybrid SPECT/CT, and sentinel lymphadenectomy. Intraoperative node detection and localization were guided by a laparoscopic gamma-probe and a portable gamma-camera. This gamma-camera was set to display both the (99m)Tc signal and the (125)I-seed signal. This (125)I seed was placed on top of the gamma-probe, functioning as a pointer on screen, thus enabling real-time sentinel node localization with the gamma-camera., Results: In 16 patients with midabdominal drainage on planar images and in 2 patients with nonvisualization on planar images, SPECT/CT showed clear localization of paraaortic sentinel nodes in relation to the abdominal vessels. Five patients underwent open surgery, and 13 patients underwent laparoscopy. The paraaortic sentinel nodes were successfully localized and removed in 15 patients with the help of the portable gamma-camera and gamma-probe and in 3 patients with the gamma-probe only. In 1 patient, the paraaortic sentinel node showed a metastasis., Conclusion: If retroperitoneal drainage is expected, SPECT/CT provides good detection and clear localization of sentinel nodes in relation to anatomic structures. Detection and removal of paraaortic sentinel nodes by means of a laparoscopic gamma-probe and real-time imaging with a portable gamma-camera is a successful method with high intraoperative detection rates.

Introduction: Early conventional lymphoscintigrams can distinguish sentinel nodes from second-tier nodes and the new SPECT/CT technology shows their precise anatomical location. The purpose of the study was to analyze lymphatic drainage patterns to the groin using these techniques and to determine the implications for a potential groin dissection., Methods: Fifty-five groins in 50 patients were analyzed using lymphoscintigrams and SPECT/CT. The superficial groin was divided in five Daseler-zones, and the pelvic region in three zones., Results: A total of 106 sentinel nodes were depicted: 10% in the superior lateral, 13% superior medial, 42% inferior medial, 26% central, and 8% in the external iliac zone. The second-tier nodes were mostly visualized in the external iliac zone (54%). No drainage at all was seen to the inferior lateral zone. In lower trunk melanoma, 81% of the sentinel nodes were in the superior and central zones, and no second-tier nodes were observed in the inferior zones. Twelve sentinel nodes were involved: ten in the inferior medial and two in the central zone., Conclusions: Most (involved) sentinel nodes were found in the inferior medial and central zones. The high frequency of pelvic second-tier nodes indicates the need for a deep completion groin dissection in the majority of patients with positive sentinel nodes. In none of the patients, lymphatic drainage was seen to the inferior lateral zone, which suggests that this area need not be included in a completion dissection. In patients with lower trunk melanoma, the inferior medial zone may not need to be removed either.

Objective: To prospectively evaluate the performance of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) to detect occult metastasis in patients with clinically node-negative (cN0) penile carcinoma, as there is little information on the use of (18)F-FDG-PET/CT in penile carcinoma., Patients and Methods: In 24 patients, scheduled to undergo dynamic sentinel-node biopsy, hybrid PET/CT was used before surgery to assess the nodal status of the cN0-groins. Six of the 24 patients were unilaterally cN0. Thus, 42 cN0-groins were evaluated for occult metastasis using PET/CT. All scans were assessed by two experienced nuclear physicians. The histopathological tumour status of the removed sentinel node was used as the standard of care to evaluate the PET/CT-results., Results: Histopathology was tumour-positive in five of the 42 (12%) evaluated cN0-groins, two of which contained only micrometastases (<2 mm). One of the five tumour-positive cN0-groins was correctly predicted on the PET/CT-images. All false-negative PET/CT scans contained metastasis of

Purpose: Our aim was to assess the feasibility of intraoperative radioguidance with a portable gamma camera during laparoscopic sentinel node (SN) procedures in urological malignancies., Methods: We evaluated the use of the intraoperative portable gamma camera in 20 patients: 16 patients with prostate carcinoma (PCC), 2 patients with renal cell carcinoma (RC) and 2 patients with testicular cancer (TC). Intra/peritumoural injection of (99m)Tc-nanocolloid ((99m)Tc) was followed by planar lymphoscintigraphy, SPECT/CT and marking of SN levels. Before laparoscopy a (125)I seed was fixed on the laparoscopic gamma probe as a pointer of SN seeking. The portable gamma camera was set to display the (99m)Tc signal for SN localisation and the (125)I signal for SN seeking. Matching of these signals on screen indicated exact SN localisation, and consequently this SN was removed., Results: The mean injected dose was 218 MBq in PCC, 228 MBq in RC and 88 MBq in TC. Pelvic SN were visualised in all PCC patients, with uncommonly located SN in seven patients. SN metastases were found in seven patients (one in a uncommonly located SN). Both RC patients and TC patients had para-aortic SN, which were all tumour free. A total of 59 SN were removed. The portable gamma camera enabled real-time SN display/identification in 18 patients (90%)., Conclusion: The use of a portable gamma camera in combination with a laparoscopic gamma probe incorporates intraoperative real-time imaging with improved SN identification in urological malignancies. This procedure might also be useful for SN identification of other deep draining malignancies.

Unlabelled: 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., Methods: (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., Results: 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., Conclusion: 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.

Unlabelled: The reliability of sentinel node biopsy is dependent on the accurate visualization and identification of the sentinel node(s). It has been suggested that extensive metastatic involvement of a sentinel node can lead to blocked inflow and rerouting of lymph fluid to a "neo-sentinel node" that may not yet contain tumor cells, causing a false-negative result. However, there is little evidence to support this hypothesis. Recently introduced hybrid SPECT/CT scanners provide both tomographic lymphoscintigraphy and anatomic detail. Such a scanner enabled the present study of the concept of tumor blockage and rerouting of lymphatic drainage in patients with palpable groin metastases., Methods: Seventeen patients with unilateral palpable and cytologically proven metastases in the groin underwent bilateral conventional lymphoscintigraphy and SPECT/CT before sentinel node biopsy of the contralateral groin. The pattern of lymphatic drainage in the 17 palpable groin metastases was evaluated for signs of tumor blockage or rerouting., Results: On the CT images, the palpable node metastases could be identified in all 17 groins. Four of the 17 palpable node metastases (24%) showed uptake of radioactivity on the SPECT/CT images. In 10 groins, rerouting of lymphatic drainage to a neo-sentinel node was seen; one neo-sentinel node was located in the contralateral groin. A complete absence of lymphatic drainage was seen in the remaining 3 groins., Conclusion: The concept of tumor blockage and rerouting was visualized in 76% of the groins with palpable metastases. Precise physical examination and preoperative ultrasound with fine-needle aspiration cytology may identify nodes with considerable tumor invasion at an earlier stage and thereby reduce the incidence of false-negative results.

Background: Sentinel node biopsy became the standard of care before consensus on the technique was reached and without randomized studies having shown a similar or decreased axillary recurrence rate. The purpose of this study was to evaluate studies reporting on patients with a negative sentinel node biopsy., Methods: We performed a systematic review and meta-analysis of the literature for studies concerning clinically node-negative breast cancer patients with a tumour-negative sentinel node biopsy and no subsequent axillary node dissection. The axillary recurrence rate was determined, as well as the sensitivity of the sentinel node procedure and the differences in lymphatic mapping techniques., Results: Forty-eight studies concerning 14 959 sentinel node-negative breast cancer patients followed for a median of 34 months were selected. Sixty-seven patients developed an axillary recurrence, resulting in a recurrence rate of 0.3%. The sensitivity of the sentinel node biopsy was 100%. Uni- and multivariable variable analyses showed that the lowest recurrence rates were reported in studies performed in cancer centres, in studies that described the use of (99m)Tc-sulphur colloid, and also when investigators used the superficial injection technique or evaluated the harvested sentinel nodes with haematoxylin-eosin and immunohistochemistry staining (p<0.01)., Conclusions: In this systematic literature review, the axillary recurrence rate in sentinel node-negative patients is 0.3%, which is well within the desired range. The median sensitivity of the procedure appears to be as high as 100%. The recurrence rate is influenced by the differences in the lymphatic mapping technique.

Background: In breast cancer patients with only extra-axillary sentinel nodes, surgeons typically perform axillary node dissection. The purpose of this study was to evaluate our approach to spare such patients further dissection based on the hypothesis that a sentinel node is not necessarily located in the axilla., Methods: Between March 11, 1999 and March 5, 2008, 1,949 breast cancer patients underwent lymphatic mapping with preoperative lymphoscintigraphy and intraoperative use of a gamma-ray detection probe and patent blue dye. The tracers were injected into the tumors., Results: Eighty-two of the 1,949 patients had only extra-axillary drainage on their lymphoscintigrams. A sentinel node was harvested from the axilla in 62 patients but not in the remaining 20 patients. No axillary lymph nodes were removed in 4 of these 20 patients, suspicious palpable nodes were excised in another 4 patients, and node sampling was done in the remaining 12. These nodes were all free of disease. All sentinel nodes outside the axilla were removed. Two patients had a metastasis in an internal mammary chain node. No lymph node recurrences were detected in or outside the axilla in any of the 20 patients with a median follow-up time of 49 months., Conclusion: 4% of the patients have only extra-axillary drainage on preoperative lymphoscintigrams. It is worthwhile to explore the axilla since a sentinel node can be found in three-quarters. In the remaining 1% without axillary sentinel nodes, axillary sampling seems unnecessary and the approach to refrain from axillary dissection appears valid.

Objective: To report experience with sentinel node (SN) lymphadenectomy which allows an assessment of the exact location of radioactive and of tumour-bearing lymph nodes, and evaluate differences in timing of the scintigraphy and surgery., Patients and Methods: The study included 35 patients who opted for external beam radiation therapy for prostate carcinoma of intermediate or poor prognosis. Agreement was reached between the participating urologists and the physicians of the nuclear medicine department on the definition of the relevant anatomical areas. The time between a transrectal intraprostatic injection with the radioactive nanocolloid and the laparoscopic SN procedure varied from 5 h to 26 h. Scintigrams were merged with the computed tomography scans until combined methods became available. A laparoscopic gamma-probe was used to identification the SNs, and an extensive laparoscopic node dissection undertaken in the same procedure. Lymph nodes were submitted to the pathologist in such a way that their exact location could be reconstructed. After surgery a graphic report was produced showing the exact location of the lymph nodes., Results: Of the 35 patients 40% were node positive; a mean of 13.5 nodes were resected, and there were no false-negative results. The location of the vast majority of the tumour-positive SNs was around the bifurcation of the external and internal iliac artery, and so involved nodes from the internal iliac, external iliac, communis and obturator basins. Of the six SNs outside the extended node dissection area, two were positive but only one of them exclusively so (lateral to the external iliac artery). The scintigrams did not change after 4 h, and the operation should be done within 24 h to have sufficient radioactivity in the nodes to be detected by the probe. There were eight complications (23%) but only one could be attributed to the SN procedure; the others were thought to be related to the extended laparoscopic node dissection., Conclusion: The laparoscopic SN procedure is a reliable tool for diagnosing prostate cancer-bearing lymph nodes, but the extended laparoscopic node dissection has, in this series and others, too many complications for it to be attractive for diagnostic purposes. The SN procedure makes an extended node dissection unnecessary in most patients.

Background: The extent of a completion groin dissection in sentinel node-positive melanoma patients was guided by the location of the second-echelon nodes on the preoperative lymphoscintigram. The purposes of the current study were to investigate the pathological findings, the lymph node recurrences and (disease-free) survival associated with this approach., Methods: Between June 1996 and April 2007, 42 patients underwent completion groin dissection after a tumor-positive sentinel node biopsy. Eighteen patients had femoro-inguinal second-echelon nodes on their lymphoscintigram and underwent a superficial lymph node dissection. Twenty-four patients had iliac-obturator second-echelon nodes found by scan and underwent a combined superficial and deep dissection., Results: The median follow-up time was 61 months. One of the 18 patients who underwent a superficial groin dissection developed a deep (obturator) lymph node recurrence after 12 months. Revision of the lymphoscintigram showed that the images had been interpreted incorrectly and that the second-echelon node was located in the obturator area after all. A combined superficial and deep dissection revealed additional involved nodes in the deep lymph node compartment in 2 of the 24 patients. At 5 years, 77% of all patients were alive, and 56% were alive and free of disease. These figures were 76% and 53%, respectively, in the patients who underwent superficial dissection only, and 80% and 61%, respectively, in the patients who also underwent deep dissection., Conclusions: This study suggests that a strategy to determine the extent of the groin dissection that is based on the location of the second-tier nodes may be valid.

Background: At our institution, tracer fluids are administered in the primary breast cancer and, in addition to the ones in the axilla, sentinel nodes outside the axilla are rigorously pursued. The objective of the present study of sentinel node-negative breast cancer patients was to determine the lymph node recurrence rates in the axilla and elsewhere, the false-negative rates, and the survival., Methods: Between January 1999 and November 2005, 1,019 breast cancer patients underwent a sentinel node biopsy. In 748 of them, 755 sentinel node biopsies did not reveal a tumor-positive sentinel node and they did not undergo axillary node dissection. Metastases were revealed in 284 sentinel node biopsies performed in the remaining 271 patients: 247 in the axilla, 20 outside the axilla, and 17 both in the axilla and elsewhere. The median follow-up duration was 46 months., Results: Two of the 748 sentinel node-negative patients developed an axillary lymph node recurrence (0.25%) and two others developed a supraclavicular lymph node recurrence (0.25%). The overall lymph node recurrence rate was 0.5%. The false-negative rates were 1.4% overall, 0.8% for the axilla, and 5.1% for the extra-axillary nodes. After five years, 95.9% of all sentinel node-negative patients were alive and 89.7% were alive without evidence of disease., Conclusion: The low recurrence and false-negative rates and promising survival figures show that our lymphatic mapping method with intralesional tracer administration is accurate for the axilla. Outside the axilla, 5.1% of involved sentinel nodes were missed.

Background: The aim was to validate the sentinel node biopsy procedure in women who had previous breast excision biopsy by means of determining the reproducibility of lymphoscintigraphy after surgery., Methods: Twenty-five women scheduled for excision biopsy of a breast lesion were investigated. The day before surgery, (99m)Tc-labelled nanocolloid was injected into the tumour. Lymphoscintigraphy was repeated a minimum of 2 weeks after surgery., Results: Preoperative lymphoscintigraphy visualized at least one sentinel node in all 25 women. Discrepancy in the drainage patterns after surgery was noted in 17 of 25 patients. A change in the drainage pattern in the axilla after excision biopsy was seen in 11 women. Drainage to the internal mammary chain was noted before surgery in 13 women, but only three had the same drainage pathways after excision biopsy., Conclusion: After breast excision biopsy lymphoscintigraphy usually showed a different drainage pattern. This implies that sentinel node biopsy should be performed before excision biopsy to ensure optimal sensitivity., (Copyright (c) 2007 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.)

Objectives: Dynamic sentinel node biopsy (DSNB) has been performed at our department since 1994 to assess status of inguinal lymph nodes of clinically node-negative (cN0) patients with penile carcinoma. Over time, several modifications were made to reduce the false-negative rate and thus increase sensitivity. We compared the false-negative and complication rates of the current procedure, as performed at our institute since 2001, with the prior procedures., Materials and Methods: The patients who underwent DSNB for penile carcinoma in the period from 1994 until July 2004 were divided into two cohorts: cohort A: patients treated from 1994 until 2001; cohort B: patients treated from 2001 until 2004. Cohort A consisted of 92 patients, in whom 157 groins were explored. Cohort B consisted of 58 patients, with a total of 105 explored groins. Medians for follow-up in cohorts A and B were 83 (range: 24-130) and 30 (range: 24-49) mo, respectively. The false-negative and complication rates were determined in both cohorts., Results: In cohort A, 21 of 157 explored groins contained tumour-positive sentinel nodes, and five false-negative procedures were encountered, resulting in a false-negative rate of 19.2%. In cohort B, 20 of 105 explored groins contained tumour-positive sentinel nodes, and one procedure was false-negative. The false-negative rate was 4.8%. The rate of complications dropped from 10.2% in cohort A to 5.7% in cohort B. All complications were minor and transient., Conclusions: The false-negative and complication rates of DSNB have decreased since the procedure was modified. The current procedure has false-negative and complication rates of 4.8% and 5.7%, respectively. DSNB has matured into a reliable and safe method for assessing status of lymph nodes in cN0 penile carcinoma patients.

Background and Objectives: The primary lymphatic pathway of patients with breast cancer is toward the axilla, but lymph drainage is also possible towards the internal mammary chain and the supraclavicular fossa. In the current article, the development of breast cancer recurrences at these two sites after sentinel lymph node biopsy is reviewed., Methods: Since 1997, 803 patients underwent sentinel lymph node biopsy with intratumoral injection of 99mTc-nanocolloid and patent blue dye in The Netherlands Cancer Institute. All sentinel nodes as visualized on the lymphoscintigraphy images were pursued. The patients were followed prospectively for a median period of 34 months. Patients with a lymph node recurrence outside the axilla were identified and their lymphatic mapping procedures were reviewed., Results: Four of the 803 patients (0.5%) developed regional lymph node recurrences outside the axilla. One recurrence was located in the internal mammary chain, the other three in the supraclavicular bed. One or two of these patients also had an axillary recurrence. The sentinel node procedure had failed in two of the four patients., Conclusion: The incidence of nodal recurrences outside the axilla is low. Although all extra-axillary sentinel nodes were pursued, some of these recurrences concern missed sentinel nodes that harbor metastasis. Identification of all sentinel nodes and subsequent treatment of the involved basins may reduce the risk of breast cancer recurrences in these unusual locations., (2005 Wiley-Liss, Inc.)

Purpose: We evaluated the reproducibility of lymphoscintigraphy in the assessment of the location and number of sentinel nodes in patients with penile carcinoma., Materials and Methods: A total of 20 patients were prospectively included in analysis. Lymphoscintigraphy was performed after intradermal injection of technetium nanocolloid around the tumor or excision scar. We performed 10-minute anterior dynamic imaging, and static anterior and lateral images were obtained at 30 minutes and 2 hours. The following day scintigraphy was repeated after a second injection of the radiolabeled colloid given in an identical fashion, preceded by acquisition of a starting image. An observer evaluated the paired images and count rates were calculated from the images., Results: At least 1 sentinel node was visualized in all patients on the first lymphoscintigram. A total of 56 sentinel nodes were seen in 38 basins. Drainage to both groins was seen in 18 patients. In 1 of these patients drainage to the prepubic area was also observed. There were 2 patients with drainage to 1 groin. The second lymphoscintigram revealed the same drainage pattern in all patients- the same number of nodal basins and number of sentinel nodes were visualized at identical locations. All hotspots that were visualized during the first lymphoscintigram showed an unequivocal increase in radioactivity after repeat injection. Thus, the reproducibility of penile lymphoscintigraphy was 100% (95% CI 85%-100%). The Pearson correlation coefficient of the paired count rates was 0.69 (p <0.0001)., Conclusions: Results of lymphoscintigraphy in patients with penile carcinoma are highly reproducible for assessment of the number and location of sentinel nodes.

An unusual sentinel node location in a patient with penile carcinoma is described. The preoperative lymphoscintigram showed a prepubic sentinel node. The node could be harvested during surgery. This case illustrates one of the advantages of lymphatic mapping in penile carcinoma: preoperative lymphoscintigraphy can identify lymph nodes outside the usual nodal basins.

Background: The aim of this study was to determine the visualization rate, identification rate, and clinical implications of biopsy of sentinel nodes in the internal mammary chain (IMC) in patients with breast cancer., Methods: From January 1999 to December 2002, 691 sentinel node procedures were performed. Preoperative lymphoscintigraphy was performed after injection of (99m)Tc-labeled nanocolloid into the tumor (.2 mL; 115 MBq; 3.1 mCi). The sentinel node was surgically identified with the aid of patent blue dye and a gamma ray detection probe., Results: The sentinel node in the IMC could be harvested in 130 (87%) of the 150 patients in whom it was visualized on the images and contained metastases in 22 (17%) of these 130 cases. In nine patients (7%), the IMC sentinel node was tumor positive, whereas the axilla was tumor-free. Stage migration was seen in all patients with a tumor-positive IMC sentinel node (17%). There was a change of management in 38 (29%) of the 130 patients: institution or omission of radiotherapy to the IMC, adjuvant systemic therapy, or omission of an axillary lymph node dissection., Conclusions: Pursuit of IMC sentinel nodes improves the staging of patients with breast cancer and enables treatment to be better adjusted to the needs of the individual patient.

Aims: The purpose of the study was to evaluate the false negative sentinel node procedures in patients with breast cancer at our institution., Methods: A total of 606 sentinel node biopsies were performed on 599 clinical N0 breast cancer patients between January 1997 and November 2001., Results: The axillary sentinel node revealed metastasis in 204 (36.1%) of the 565 patients in whom it was identified and was false negative in eight patients. Two false negative results came to light by confirmatory axillary lymph node dissection during the learning phase. Tumour-positive lymph nodes were incidentally found in the axillary tail of the simple mastectomy specimen in two patients. Excision of a firm, non-radioactive, unstained but tumour-positive non-sentinel node occurred in three other patients. One patient developed an axillary recurrence 22 months postoperatively. Presumptive causes were surgical delay, pathological sampling error and tumour blocking., Conclusion: Intra-operative palpation of the axilla to identify suspicious lymph nodes is recommended. In a two-day protocol, surgery should be performed first thing in the morning. Seven slices of 50-150-micro m strike an acceptable balance between sensitivity and work load for the pathologist.

A 1.5-cm nonpalpable mass was detected in the upper outer quadrant of the left breast by screening mammography in a 55-year-old woman. The patient was scheduled for a sentinel node procedure, and lymphoscintigraphy was performed the day before surgery. Unintentionally, she received an intraparenchymal tracer injection 3 cm away from the malignant lesion instead of the intended intratumoral injection. Lymphoscintigraphy revealed two sentinel nodes in the axilla. A second dose of Tc-99m nanocolloid was injected the next day into the primary tumor through a catheter that had been inserted under ultrasound guidance the previous day. Once more, a lymphoscintigraphic image was obtained that showed additional sentinel nodes in two different regions outside the axilla. This observation supports the authors' contention that lymphatic watersheds exist in the breast and highlights the importance of tracer administration into or close to the tumor.

Background and Purpose: An accurate internal mammary (IM) lymph node localization technique is required for proper irradiation of the IM lymph nodes in breast cancer patients. In this study the measurement accuracy of three techniques for direct or indirect localization of the IM nodes was estimated., Materials and Methods: In 40 patients the IM lymph node depth and lateral distance from the patient midline were measured with lymphoscintigraphy in intercostal spaces 2, 3 and 4. The corresponding position of an IM vessel was measured with sonography and CT in intercostal spaces 1-4. The sonography and CT vessel measurements in the four intercostal spaces were compared to determine the measurement accuracy of sonography. The node and vessel data in intercostal space 2 were inserted into a mathematical model to determine the measurement accuracy of lymphoscintigraphy and CT for node detection., Results: Vessel depths measured by sonography were systematically too shallow and the lateral vessel position could not be accurately determined. The mathematical model showed that the node depth and lateralization in one intercostal space can be measured directly by lymphoscintigraphy within an accuracy (1 SD) of 5 mm in depth and 6 mm in the lateral direction. The accuracy of CT for indirect node detection was 6 mm in depth and 7 mm in the lateral direction., Conclusions: Sonography is not a suitable technique for measuring the IM vessel or node position. Lymphoscintigraphy and CT have measurement accuracies for node detection that are acceptable for radiotherapy.

The aim of this study was to investigate the feasibility of lymphoscintigraphy for sentinel node identification in testicular cancer. Five patients with clinical stage I testicular cancer were prospectively included. A single dose of technetium-99m nanocolloid (mean dose 99 MBq, volume 0.2 ml) was injected into the funiculus in the first patient and into the testicular parenchyma in the following four patients. Dynamic lymphoscintigraphy was performed over 10 min, followed by early and late static images after 15 min and 2 to 24 h, respectively. Lymphoscintigraphy was followed by laparoscopic sentinel node biopsy on the same day in the last two patients using patent blue dye and an endoscopic gamma probe. The funicular administration route showed five hot spots in the right inguinal region after 2 h. Intratesticular administration resulted in sentinel node visualisation in three of the four patients. Dynamic images showed afferent lymphatic vessels to one sentinel node in the left para-aortic region in two patients and two sentinel nodes in the left para-aortic region in another patient. Sentinel nodes were intraoperatively identified in one of two patients who underwent laparoscopic exploration. It is concluded that lymphoscintigraphy for sentinel node identification is feasible in stage I testicular cancer using intratesticular radiocolloid administration.

Background: The purpose of this study was to determine the feasibility of both lymphatic mapping and probe-guided primary tumor excision by use of intralesional tracer administration in clinically occult breast cancer., Methods: Sixty patients with a clinically occult breast lesion were prospectively included. Lymphoscintigraphy was performed after intratumoral injection of 99mTc-labeled nanocolloid guided by ultrasound or stereotaxis. A catheter over a localization wire was inserted for intraoperative blue dye administration by using the same imaging techniques. After sentinel node identification, the gamma-ray detection probe was used for radio-guided wide local excision in patients who underwent breast-conserving therapy., Results: A sentinel node was visualized on the scintigrams in 56 patients (93%) and could be identified intraoperatively in 58 patients (97%). A sentinel node contained tumor in 10 (17%) of these patients. Extra-axillary sentinel nodes were visualized in 43%, were collected in 38%, and contained metastasis in 7% of the patients. Complete excision of the primary tumor could be accomplished in 39 (87%) of 45 patients., Conclusions: Both sentinel node biopsy and probe-guided excision of a nonpalpable breast cancer is feasible with the aid of intralesional tracer administration. Sentinel node metastasis was found in 17% of the patients. A remarkably high percentage of extra-axillary drainage (43%) was observed.

Lymphatic mapping with selective lymphadenectomy requires a concerted effort from the nuclear medicine physician, surgeon, and pathologist. Application of preoperative lymphoscintigraphy, and intraoperative use of both a gamma detection probe and a vital dye are recommended. This combined approach increases the likelihood of finding all sentinel nodes without removing nonsentinel nodes. A literature review of current experience reveals that the sentinel node can be found in more than 90% of the patients. When confirmatory lymphadenectomy follows, the false-negative rate can be kept down to about 5% after a certain learning phase. The sensitivity of this novel approach to detect lymphatic dissemination is currently overestimated because lymph node metastases in patients with a tumor-free sentinel node are probably overlooked. This shortcoming will be compensated by the more accurate pathologic evaluation of a sentinel node and the finding of sentinel nodes outside the axilla. Therefore the procedure is probably adequate and safe in patients at low risk of having disseminated disease. Lymphatic mapping with sentinel node biopsy is rapidly becoming the standard of care.

Faint lymph uptake may hamper sentinel node (SN) identification by scintigraphy and subsequent gamma probe localization. The aim of the present study was to evaluate an adjustment in the colloid particle concentration and tracer dosage to optimize mammary lymphoscintigraphy. Scintigraphy was performed in 151 patients with a palpable breast carcinoma and clinically negative axilla: for the first 75 patients (group A) a standard labelling of 0.5 mg nanocolloid with 99Tcm was performed, for the subsequent 76 patients (group B) the labelling dilution volume was reduced from 4 to 2 ml. For both groups the volume of injection was 0.2 ml. Lymph node uptake was evaluated by a 4-step visual score (from 0 = absent to 3+ = very intense), and by count quantification of at 4 h in the first draining SN. The SN visualization rate increased from 93% (70/75) in group A (mean dosage 93.4 MBq, range 57-130 MBq) to 99% (75/76) in group B (mean dosage 106.5 MBq, range 74-139 MBq). The percentage of patients with uptake 3+ was significantly higher (P = 0.001) in group B (51% vs 35% in group A). SN counts were significantly higher for group B (P<0.001). The percentage of patients with less than 2000 counts/node diminished from 45% in group A to 9% in group B (P = 0.001). In group B (P = 0.033) more lymph channels (53% vs 35% in group A) were visualized and for a longer time (26% vs 4% at 4 h). Axillary drainage was seen in 96% in group A and 98% in group B whereas non-axillary drainage was observed in 19% and 25%, respectively. Intraoperative SN identification rate was 97% in group A and 100% in group B. SN metastases were found in 41% of group A and 47% of group B. It is concluded that enhancement of colloid particle concentration and adjustment of tracer dosage led to improved SN identification by substantial increase in lymph node uptake and lymph vessel depiction. A significant reduction of cases with faint SN uptake enables better surgical efficacy.

Lymphoscintigraphy for sentinel node (SN) identification has been extensively validated in breast cancer and melanoma. The aim of this study was to evaluate the findings of lymphoscintigraphy for SN identification in carcinoma of the penis. Lymphoscintigraphy was performed in 74 consecutive patients (mean age 62.2 years, range 28-87 years) with clinically lymph node-negative squamous cell carcinoma of the penis (stage T2 or greater). Following local anaesthesia by xylocaine 10% spray, technetium-99m nanocolloid (mean dose 64.8 MBq, range 40-131 MBq) in a volume of 0.3-0.4 ml was injected intradermally around the tumour. Shortly after injection, a 20-min dynamic study was performed with a dual-head gamma camera; subsequently, static anterior and lateral images were obtained at 30 min and 2 h using simultaneous cobalt-57 flood source transmission scanning. 57Co-assisted skin marking defined SN location for gamma probe/blue dye-guided biopsy, which was performed the next day. The SN visualization rate was 97% (72/74). Lymphatic drainage was bilateral in 81% of the cases (58/72), exclusively to the left groin in 13% (9/72) and only to the right groin in 6%. Bilateral lymph node drainage was synchronous in 38% (22/58) and asynchronous in 62% (in 18 patients the initial route was the left groin, and in the other 18, the right groin). Visualization before 30 min occurred in 66 patients (93%), in 64 of them (88%) already during the dynamic study. A total of 173 SNs were visualized (85 in the right groin, 88 in the left groin). Pitfalls were caused by inguinal skin contamination during injection (four patients) and intracavernous administration (one patient). At surgery, a total of 161 SNs were identified and removed. Sixteen patients (22%) had a tumour-positive SN and underwent standard regional lymph node dissection subsequently. During follow-up (median 28 months, range 3-74 months), two patients with a negative SN developed lymph node metastases in the mapped basin. It is concluded that penile lymphoscintigraphy is a valid and well-tolerated method for lymphatic mapping and SN identification. Although bilateral early inguinal drainage is the most frequent pattern, late imaging is recommended principally in patients with initial unilateral drainage in order to exclude delayed lymph node filling in the contralateral groin. SN identification may lead to a more accurate staging and avoid extensive lymph node dissection in the majority of patients with penile carcinoma.