Radioactive Colloid Research Articles

Optimization of a gamma imaging probe for axillary sentinel lymph mapping

Sentinel lymph node (SLN) mapping is a technique for assessing whether early-stage invasive breast cancer has metastasized, thus determining prognosis and treatment options. SLN identification is achieved using the blue-dye and radioactive colloids techniques, which are sometimes combined with lymphoscintigraphy. Furthermore, intra-operative gamma acoustic probes, as well as gamma imaging probes are used during surgery. The purpose of this study is the construction of a gamma probe for sentinel lymph node imaging and its optimization in terms of sensitivity with respect to spatial resolution. The reference probe has small field of view (2.5 × 2.5 cm2) and is based on a position sensitive photomultiplier tube (PSPMT) coupled to a pixellated CsI(Tl) scintillator. Following experimental validation, we simulated the system using the GATE Monte Carlo toolkit (GATE v6.1) and modeled various collimator geometries, in order to evaluate their performance and propose the optimal configuration. The constraints of the proposed gamma imaging probe are i) sensitivity close to 2 cps/kBq and ii) spatial resolution equal to 6 mm at 2 cm source-to-collimator distance and ∼ 10 mm at 5 cm. An integrated structure that achieves those requirements is a tungsten collimator with 2 × 2 mm2square holes, 16 mm thickness, 0.15 mm septa, where each CsI(Tl) 2 × 2 × 5 mm3 crystal pixel is placed inside the collimator.

Impaired Gastric Emptying and Small Bowel Transit in Children With Mitochondrial Disorders

The primary aim of our study was to evaluate gastric emptying (GE) and intestinal transit time (ITT) in children with mitochondrial disorders (MD), and secondarily to evaluate the effect of prokinetics in those with prolonged GE. We enrolled subjects 3 to 18 years with MD and having any of the following gastrointestinal (GI) symptoms: abdominal pain, vomiting, constipation, diarrhea, or gastroesophageal reflux. Abdominal pain was scored by visual analog pain scale (1-10). Age-appropriate diet was labeled with radioactive technetium-99 sulfur colloid and its movement tracked along the GI tract. Delayed GE based on our institutional standards was defined as half emptying time >90 minutes for a solid and >60 minutes for a semisolid meal. Prolonged ITT was defined as >4 hours for the tracer to pass from mouth to cecum. A prokinetic was instituted to those with delayed GE, and the study was repeated if possible in 4 to 8 weeks. Of the 26 subjects, 18 (69%) had delayed GE (median GE 99 minutes) and 12 (46%) had prolonged ITT. The study was repeated in 9 subjects after administering a prokinetic for >1 month. GE normalized in only 3 subjects (median GE on treatment 128 minutes). Mean abdominal pain score, which was 4.8 (max 10) in the 9 subjects, did not improve (5.6 after prokinetic therapy). A high prevalence of delayed GE and prolonged ITT was seen in children with MD having GI symptoms, and these abnormalities were poorly responsive to prokinetic therapy.

The management of diffuse-type giant cell tumour (pigmented villonodular synovitis) and giant cell tumour of tendon sheath (nodular tenosynovitis)

Giant cell tumours (GCT) of the synovium and tendon sheath can be classified into two forms: localised (giant cell tumour of the tendon sheath, or nodular tenosynovitis) and diffuse (diffuse-type giant cell tumour or pigmented villonodular synovitis). The former principally affects the small joints. It presents as a solitary slow-growing tumour with a characteristic appearance on MRI and is treated by surgical excision. There is a significant risk of multiple recurrences with aggressive diffuse disease. A multidisciplinary approach with dedicated MRI, histological assessment and planned surgery with either adjuvant radiotherapy or systemic targeted therapy is required to improve outcomes in recurrent and refractory diffuse-type GCT. Although arthroscopic synovectomy through several portals has been advocated as an alternative to arthrotomy, there is a significant risk of inadequate excision and recurrence, particularly in the posterior compartment of the knee. For local disease partial arthroscopic synovectomy may be sufficient, at the risk of recurrence. For both local and diffuse intra-articular disease open surgery is advised for recurrent disease. Marginal excision with focal disease will suffice, not dissimilar to the treatment of GCT of tendon sheath. For recurrent and extra-articular soft-tissue disease adjuvant therapy, including intra-articular radioactive colloid or moderate-dose external beam radiotherapy, should be considered.

Diagnosis of axillar lymph node status and sentinel node biopy (SNB) by indocyanin green (ICG) fluorescence imaging in early breast cancer patients.

e11503 Background: In breast cancer patients, diagnosis of Axillar lymph node (Ax LN) status is practical use in deciding treatment strategy. But, diagnostic methods are different by different institution. The purpose of this study was to review diagnostic methods of Ax LN status. Methods: From December 2006, 483 cases were underwent breast cancer operation and within 356 (74%) clinical node negative primary breast cancer cases underwent Sentinel Node biopsy (SNB) by indocyanine green (ICG) fluorescence imaging. Dye was injected sub dermal in the areola. After one minute massage, subcutaneous lymphatic channel draining from the areola to the axilla was observed by Image processing and measuring system (PDE C9830, Hamamatsu Photonics Co). Skin incision was done at the point which fluorescence imaging disappeared (ASCO2011, Electronic Publication only). From September 2010, Aspiration Biopsy Cytology (ABC) of Ax LN (LN-ABC), Ultrasonography (US) and CT were done as routine workup in breast cancer patients. Node positive cases were received pre-operative chemotherapy or Ax LN dissection and node negative cases were underwent SNB by ICG fluorescence imaging during operation. Results: From December 2006, SNB were done 356 clinical node negative primary breast cancer cases. SN was detected 342 cases, detective rate was 96 %. This rate was as good as SNB done by radioactive colloid (Phytate radiolabelled by Tc98) with dye (detective rate was 95%, ASCO2011). The lymph node metastasis was detected 48 cases (14%). From Sep 2010 to Oct 2011, LN-ABC was done 49 cases of the 142 primary breast cancer patients. Fourteen cases were LN-ABC positive and 35cases were LN-ABC negative. Positive SNB were detected 3 of the 35 cases (2 cases had micro metastasis and one case had macro metastasis). Within three SNB positive cases, pre-operative US and CT had no positive finding. Positive LN-ABC cases (14 cases) were received pre-operative therapy or Ax LN dissection. Conclusions: These results suggest that LN-ABC was useful procedure detecting positive Ax LN and SNB by ICG fluorescence imaging was useful and easy tool in operative breast cancer patients.

Technetium-99m sulfur colloid (TSC) as a phenotypic probe for predicting pharmacokinetics (PK) and palmar-plantar erythrodysesthesia (PPE) toxicity of pegylated liposomal doxorubicin (PLD) in patients (pts) with recurrent epithelial ovarian cancer (EOC).

5050 Background: There is significant variability in the PK and PD (efficacy and toxicity) of PLD. Clearance (CL) of PLD has been proposed to occur primarily via uptake by cells of the mononuclear phagocyte system (MPS) mainly located in the liver, spleen, and blood. TSC is a radioactive colloid used clinically for diagnostic and functional imaging of the MPS. Our aim is to evaluate TSC as a phenotypic probe of MPS activity, which may predict PLD PK and PPE toxicity in pts (n=9) with EOC. Methods: Prior to administration of PLD on cycle 1 day 1 (C1D1), TSC was administered at 10 mCi IVP × 1. Dynamic planar and SPECT/CT images of the liver, spleen and hands were acquired using a gamma camera. Blood samples were collected up to 60 min after TSC and analyzed for radioactivity using a gamma counter. On C1D1, PLD was administered at 40 mg/m2 alone or at 30 mg/m2 in combination with carboplatin IV over 1 to 3 h. Serial PK samples were obtained from 0h to 672h post PLD dose. Plasma was processed to measure encapsulated and released doxorubicin (dox) using solid phase separation and HPLC. CL of PLD and TSC were calculated by non-compartmental analysis. The grade of PPE toxicity was determined by NCI CTCAE (v4.03) criteria. Results: Nine patients have undergone TSC imaging and eight patients completed TSC blood PK and PLD plasma PK studies. There was a positive linear relationship between TSC CL and encapsulated dox CL (R2 = 0.61, p=0.02). When patients were subdivided, there was a stronger relationship between TSC CL and encapsulated dox CL (R2 = 0.81, p=0.03) in pts receiving PLD monotherapy. A positive relationship using Spearman’s correlation (ρ=0.84, p=0.006) was also found between maximum grade PPE toxicity developed and estimated AUC of encapsulated dox in hands [(TSC AUCBlood)/(TSC AUCHand)*Encapsulated Dox AUCPlasma]. Conclusions: These results suggest that TSC is a probe for MPS function and PLD PK and PD and may be used to individualize PLD therapy in pts with EOC. In addition, our findings suggest TSC may be able to predict the development of PPE in patients.

Evaluation of mobile gamma camera imaging in sentinel lymph node biopsy for melanoma independent of pre-operative lymphscintigraphy.

e19062 Background: Sentinel lymph node biopsy (SLNB) is the standard method for staging cutaneous melanoma and involves identifying the first node(s) draining a tumor, by detecting an intradermally-injected radioactive colloid tracer. Intra-operatively the sentinel node(s) are identified with a hand-held gamma probe. Pre-operative lymphoscintigraphy is obtained to identify draining lymph node basins, but requires coordinating schedules between nuclear medicine and the operating room. A pilot study utilizing Mobile Gamma Camera (MGC) devices in conjunction with conventional lymphoscintigraphy for intraoperative sentinel node localization provided clinical benefit in 20% of patients. However, utilizing MGC devices to localize lymph node basins at the time of surgery independent of conventional lymphoscintigraphy with a fixed gamma camera (FGC) has not been adequately studied. Here, we present the results of a clinical trial utilizing MGC devices to localize lymph node basins in a manner blinded to the FGC images in order to compare the modalities directly. Methods: In 2011-12 18 patients underwent Tc99 sulfur colloid lymphoscintigraphy, and MGC survey immediately pre-operative by the study surgeon. The study surgeon established an operative plan using the MGC survey, while blinded to lymphoscintigraphy results. SLNB was then performed with use of a gamma probe and intra-operative MGC imaging. Results: 22 lymph node basins were detected in 18 imaged patients by lymphoscintigraphy. All of these basins were identified by the study surgeon using the MGC device in the pre-operative setting prior to un-blinding. In every case the operative plan established based on pre-operative MGC imaging was confirmed by the FGC images. In two cases, additional information from the MGC images aided surgical decision-making. 5 of 22 lymph node basins were positive for metastasis. All of these basins were identified by pre-operative MGC imaging, and all individual positive nodes were identified by intra-operative MGC imaging. Conclusions: Pre-operative MGC imaging in sentinel lymph node biopsy can provide comparable information for operative planning, compared to standard FGC imaging.

A retrospective cohort study of cancer incidence among patients treated with radiosynoviorthesis

Radiosynoviorthesis (RS) is an intra-articular injection of a radioactive colloid for the treatment of synovitis administered most often to patients with rheumatoid arthritis or haemophilia. Although highly cost-effective in comparison with surgical or arthroscopic synovectomy, the risk of cancer associated with this treatment is not well known. We evaluated the incidence of cancer in a group of patients treated with RS. A cohort of 2412 adult patients with a variety of underlying conditions (mainly rheumatoid arthritis) and treated with at least one RS between January 1976 and December 2001, was recruited from two centres in Montréal. Cancer incidence and mortality data for cohort members over that time period were obtained from regulatory agencies using linkage. Background rates for all and specific types of cancer were obtained for the provincial (Québec) and national (Canada) population according to age, gender and calendar period categories. Category-specific rates in the cohort were compared with rates in similar categories from the general population generating standardized incidence ratios (SIR). The effects of specific isotope doses and of number of RS treatments were analysed using a Cox-regression model. No increase in the risk of cancer was observed (SIR 0.96; 95% confidence interval 0.82-1.12). There was no dose-response relationship with the amount of radioisotope administered or number of RS treatments. The study provides some indication for the safety of the procedure but homogenous diagnostic groups of younger patients (such as haemophilic patients) receiving RS will need more evaluation.

Predictors of non-sentinel lymph node metastasis in breast cancer patients with positive sentinel lymph node (Pilot study)

Background: Sentinel Lymph Node Biopsy (SLNB) procedure was found to be an accurate method of staging the axilla in patients with early stage breast cancer. The standard of care for breast cancer patients with positive SLN metastasis includes complete Axillary Lymph Node Dissection (ALND). However, in 40–70% of patients, the SLN is the only involved axillary node. Factors predicting non SLN metastasis should be identified in order to define subgroups of patients with positive SLN in whom the axilla may be staged by SLNB alone.Objectives: To identify the factors predicting metastatic involvement of the non-SLNs in breast cancer patients having SLN metastasis.Patients and Methods: Data were collected and analyzed from 80 patients with early stage invasive breast cancer (T1, T2, N0, M0) who underwent SLNB at the Surgical Oncology Department, Kuwait Cancer Control Center (KCCC) between November 2004 and February 2009. SLNB was performed using a combined technique (radioactive colloid, and blue dye) in the majority of cases. In some cases, only one technique was used. Complete ALND was performed in the case of failure of SLN identification and in patients with positive SLN. Multiple variables (patient, tumor, and SLN characteristics) were tested as possible predictors of nonsentinel lymph node metastasis.Results: The mean age of patients at diagnosis was 46.6years. The median tumor size was 2cm. The SLN identification rate was 96.2% (77 out of 80 patients). The SLN was positive in 24 patients (31%), and half of these showed evidence of capsular invasion. The median number of SLNs removed was two. The median number of positive SLNs was one. The incidence of non-SLN metastasis associated with positive SLN was 50% (12 out of 24 patients). Lymphovascular invasion was found to be the only factor associated with non-SLN metastases. In addition, two trends were observed, though they did not reach the statistical significance: the first is that the majority of patients having capsular invasion of the SLN (8 out of 12 patients, 67%) had positive non-SLN metastasis, and the second is that the patients having more than one SLN metastasis were more likely to have non-SLN metastasis (4 out of 5, 80%).Conclusion: In the current pilot study, only the lymphovascular invasion in the area of the primary tumor was found to be significantly related to the nonsentinel lymph node metastasis. There was a tendency toward higher incidence of nonsentinel lymph node metastasis associated with the number of positive SLN and capsular invasion of SLN, though this did not reach the statistical significance. This could be attributed to the small number of patients recruited. Further evaluation of the predictors of nonsentinel lymph node metastasis on a larger number of patients is required. The validation of these predictors in prospective studies may enable approximately half of early stage breast cancer patients with positive SLN to be staged with SLNB alone while avoiding the morbidity of unnecessary ALND.

P3-07-38: Selective Omission of Blue Dye in Patients Undergoing Sentinel Lymph Node Biopsy for Breast Cancer.

Abstract Background Combined blue dye and radioisotope colloid injection with scintigraphy is standard practice for mapping and biopsy of sentinel lymph node in breast cancer within the UK. Whilst this combination aids sentinel node detection rate, blue dye has a number of possible adverse effects including anaphylaxis (reported as 1–3% of patients), semi-permanent skin tattooing and staining of bodily fluids which may cause distress for the unwary patient. It can also cause obscuration of the operating field, making identification and dissection of planes more difficult. Methods: Patients undergoing sentinel lymph node biopsy (SLNB) using either a combination of blue dye and radioactive colloid, or radioactive colloid alone during a 14 month period were compared for identification rate, node harvest number and final positive rate. A total of 122 axillary sentinel node biopsies in 121 patients were identified. All patients scheduled for sentinel lymph node biopsy had intradermal injection of radiocolloid and lymphoscintigram preoperatively and were checked for radioactive intensity with gamma probe on the table before draping for surgery. Patients with good signal proceeded to surgery without blue dye. Those with more than 3 nodes (n=9), radioisotope skin contamination (n=2), absent signal on scintigraphy (n=7) and/or with weak pre-operative radioactive signal (n=22) were given 2 millilitres of patent V dye subdermally in the periareolar region. Sentinel node biopsy then proceeded in the standard fashion. Data was also collected from the year prior to be used as a control group, where the combination of blue dye and radioisotope was used for all patients (n=90), and compared with the group receiving radioisotope alone. Results: The rate of identification for single agent and dual agent was 100% and 97.5% respectively, with no significant difference in mean node harvest using radioisotope alone (1.80) as compared to combined technique (1.87 p= 0.88, 95%CI −0.39 to 0.34). There was no significant difference in the number of patients with positive nodes on final histology when using single agent (13 (14%)) when compared to the dual agent technique (10 (25%) p=0.21). There was also no difference in the rate or number of node harvest in the group who underwent the single agent technique when compared to the control group (100% identification, mean harvest 1.84, p=0.77, 95% CI −0.36 to 0.27), with no difference in node positivity (16 (17%) p=0.68). No intra operative adverse reaction was reported in any of the groups. Discussion: This study has shown no significant difference in the localisation rate when selectively omitting blue dye in suitable patients compared to the combined technique. This may be due to significant operator experience or change in the method of radioisotope injection since initial studies were performed. In this study, 86 out of 126 SLNB proceeded without blue dye, meaning not only a reduction in the number of patients with minor adverse effects, but also a potential reduction in severe adverse reaction of 68% or 2 patients per year within this breast unit. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-07-38.

P3-07-25: Sentinel Lymph Node Mapping in Breast Cancer after Primary Chemotherapy.

Abstract Background The High false negativity rate and the possible of interference of primary systemic treatment (PST) and biopsy on the lymphatic drainage in the breast and axilla are the disadvantages of sentinel lymph node biopsy (SNB) after PST. The primary aim of our study was to evaluate success rate for identification and isolation of sentinel lymph node (SLN) in patients treated with PST. Secondary aims were to verify if chemotherapy and biopsy can really alter the lymphating drainage, and to identify biological and clinical factors that can influence the accuracy of this technique. Methods: Between June 2000 and April 2007, 176 consecutive operable or locally advanced breast cancer patients (T1-4N0-1M0) treated with antracyclin-based PST were enrolled in this single Institution study. Before performing a surgical biopsy and starting the treatment a lymphatic mapping was performed and the skin projection of the SLN location was then marked with permanent ink, with the aim to verify if the SLN marked did not change after biopsy and PST. Results: The SLN was removed in 164 patients, with an identification rate of 93.2% (95% confidence interval (CI) = 89.4−96.9%). Fifty patients (30.5%) had metastatic involvement at SNB, and in 21 (42.0%) of them the SLN was the only positive node. Nine patients (5.5%) had a false negative SLN. The false-negative rate was 15.3% (95% CI = 7.1−32.9%). The SNB revealed a sensitivity of 84.7% (95% CI = 73.0−96.4%), an accuracy of 94.5% (95% CI = 90.1−99.0%) and a negative predictive value of 92.1% (95% CI = 85.8−98.4%). In 163 patients (99.4%) the SLN marked at baseline was the same removed at the end of treatment, while only in 1 case (0.6%) a different SLN was identified by the lymphatic mapping performed with radioactive colloid. According to clinical and tumor characteristics the rate of identification and removal of SNB was higher in patients aged <50 (95.6%) vs >50 (91.6%), with clinical node negative (95.1%) vs positive (88.6%) and with lower grade G2 (98.0%) vs G3 (91.2%). False negative rate of SNB was higher in patients aged >50 (17.9%) vs <50 (10.0%) and with clinical node negative (17.1%) vs positive (12.5%). Lymph node involvement was significantly associated with baseline ER positivity (p=0.00595 Chi-square test). Conclusion: The identification rate, sensitivity and accuracy do not differ from other study of SNB after PST. The false-negative rate is still high and we are performing analysis to identify biological and clinical features that can influence the accuracy of this technique. To our knowledge this is the first study with an in vivo demonstration that chemotherapy and biopsy do not alter the lymphatic drainage of the breast. We are perfoming exploratory analyses to evaluate the influence of false-negative rate of SNB on overall survival (OS) and progression free survival (PFS). Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-07-25.

Breast cancer sentinel lymph node mapping using near infrared guided indocyanine green and indocyanine green–human serum albumin in comparison with gamma emitting radioactive colloid tracer

AimsRecently, a novel method of using near infrared (NIR) guided indocyanine green (ICG) and ICG conjugated with human serum albumin (ICG:HSA) for sentinel lymph node biopsy (SLNB) of breast cancer patients has shown true potential. The aim of this study was to compare the usefulness of NIR guided ICG and ICG:HSA against the gamma emitting radiocolloid (RC). MethodsA group of 49 consecutive breast cancer patients underwent SLNB using RC. From this group, the first 28 patients were compared against ICG, while the next 21 patients were compared against ICG:HSA. The number of patients with visible fluorescent path was recorded. Furthermore, the number of SLNs detected by fluorophores percutaneously and total number of intraoperative SLNs detected by fluorophores and/or RC was noted. ResultsNIR guided real time lymphatic flow was observed in 47/49 patients (96%). In all cases except one, SLNs detected by the RC tracer were also detected by their respective fluorophore. Additionally, ICG detected 10 additional SLNs in 8 patients, while 3 additional SLNs were detected by ICG:HSA in 3 patients. Statistical analysis revealed no difference between the number of SLNs detected between ICG versus ICG:HSA and RC versus ICG:HSA. However, a significant statistical difference was observed between RC and ICG (p=0.0117), as well as between the combined NIR guided and RC method (p=0.0033). ConclusionsIn conclusion, the use of either ICG or ICG:HSA with RC to obtain SLNB seems to be an effective alternative. Compared to RC alone, the use of ICG:HSA, more so than ICG alone, may provide additional benefits.

In vivo quantitative evaluation of the transport kinetics of gold nanocages in a lymphatic system by noninvasive photoacoustic tomography.

Sentinel lymph node (SLN) biopsy has emerged as a preferred method for axillary lymph node staging of breast cancer, and imaging the SLN in three-dimensional space is a prerequisite for the biopsy. Conventional SLN mapping techniques based on the injection of an organic dye or a suspension of radioactive colloids suffer from invasive surgical operation for visual detection of the dye or hazardous radioactive components and low spatial resolution of Geiger counters in detecting the radioactive colloids. This work systematically investigates the use of gold nanocages (AuNCs) as a novel class of optical tracers for noninvasive SLN imaging by photoacoustic (PA) tomography in a rat model. The transport of AuNCs in a lymphatic system and uptake by the SLN were evaluated by PA tomography on the axillary region of a rat. Quantification of AuNCs accumulated in the lymph node was achieved by correlating the data from PA imaging with the results from inductively coupled plasma mass spectrometry. Several parameters were systematically evaluated and optimized, including the concentration, size, and surface charge of the AuNCs. These results are critical to the further development of this AuNC-based PA tomography system for noninvasive SLN imaging, providing valuable information for metastatic cancer staging.

Magnetic Resonance Imaging to Guide Surgical Practice

Magnetic resonance (MR) imaging can provide functional and anatomical information in a single non-ionising examination and represents a rapidly expanding area of innovation and technology research. The lymphatic system is a complex network of lymph vessels, nodes and organs, and is essential for the maintenance of fluid homeostasis and immunocompetence. Failure of lymph clearance from the limb can be caused bycongenital absence of lymph vessels or valve incompetence, which are relatively uncommon compared to acquired obliteration of the lymph vessels (infection, trauma, radiotherapy) and obstruction of the lymph nodes by primary and secondary malignant disease, and nodal hilar fibrosis. Adequate imaging of the lymphatic system in the lower limbs should therefore be able to delineate the anatomy of the lymph vessels and nodes, both proximal and distal to the area of interest, and also provide functional information on the rate of lymph clearance. X-ray lymphangiography was one of the first techniques developed to visualise the lymphatics. 1 Patent blue dye is first injected subcutaneously into each of the web spaces in the foot (visual lymphangiography), to stain and localise the deep lymphatic vessels. The skin on the dorsum of the footis then incised and a large lymph vessel is cannulated. Oily X-ray contrast medium is injected directly into the lymph vessel and serial images are acquired; initial images show the lymph vessels whereas later ones delineate the lymph nodes. Abdominal films are required for the iliac and aortic lymph nodes and a chest film to assess the thoracic duct. This technique can give high spatial resolution anatomical and functional information, however it is hampered by: the use of ionising radiation; a single vessel is cannulated and so only some of the lymph vessels are shown; the 2D acquisition is a projection and therefore some vessels may be superimposed on others; the procedure is relatively invasive; the injected contrast media may cause inflammation and fibrosis of the lymph vessels; pulmonary complications such as pulmonary embolus and adult respiratory distress syndrome have been reported; and the contrast media may take several years to be removed from the body. 2e4

Sentinel node biopsy (SNB) by indocyanin green (ICG) fluorescence imaging in patients with operative breast cancer.

e11507 Background: Sentinel node biopsy (SNB) is standard method of breast cancer operation. There are two methods in detecting SNB using dye only and radioactive colloid with dye in Japan. We evaluated usefulness of SNB by indocyanin green (ICG) fluorescence imaging in operative breast cancer patients, retrospectively. Methods: From December 2006 to December 2010, 360 cases underwent breast cancer operation and within 253 (70%) casesin clinical node-negative cases underwent SNB by ICG fluorescence imaging. Dye was mixed 1ml ICG and 4ml Indigocarmine. Dye was injected subdermal in the areola. After one minute massage, subcutaneous lymphatic channel draining from the areola to the axilla was observed by Image processing and measuring system (PDE C9830, Hamamatsu Photonics Co). Skin incision was done at the point which fluorescence imaging disappeared. Results: SN was detected 238 cases, detective rate was 96%.The lymph node metastasis was detected 37 cases (15%). Author has been belonged at another hospita...

Technetium-99m sulfur colloid (TSC) as a phenotypic probe for the pharmacokinetics (PK) and pharmacodynamics (PD) of pegylated liposomal doxorubicin (PLD) in patients (pts) with recurrent epithelial ovarian cancer (EOC).

2582 Background: There is significant inter- and intra-patient variability in the PK and PD (efficacy and toxicity) of PLD in pts with EOC and other malignancies. This has been attributed to age and gender, but more specifically, may be related to the mononuclear phagocyte system (MPS). Clearance (CL) of PLD has been proposed to occur primarily via uptake by monocytes, dendritic cells, and macrophages mainly located in the liver, spleen, and blood. TSC is a radioactive colloid used clinically for diagnostic and functional imaging of the MPS. Our aim is to evaluate TSC as a phenotypic probe of MPS activity, which may predict PLD PK and PD in pts with EOC. Methods: Prior to (day -7 to -1) administration of PLD on cycle 1 day 1 (C1D1), TSC was administered at 10 mCi IV × 1. Dynamic planar and SPECT/CT images of the liver and spleen were acquired using a gamma camera. Blood samples were collected up to 60 min after TSC and analyzed for radioactivity using a gamma counter. On C1D1, PLD was administered at 40 mg/m2 alone or at 30 mg/m2 in combination with carboplatin IV over 1 to 1.5 h. Serial blood samples were collected up to 28 days after PLD. Plasma samples were processed to measure encapsulated (encap) and released doxorubicin via HPLC with fluorescence. Results: Six pts have undergone TSC imaging and blood PK, and PLD plasma PK studies. Mean ± SD encap doxorubicin CL and TSC CL were 25.4 ± 4.1 mL/h and 18.9 ± 5.4 mL/h, respectively. There was a positive linear relationship between TSC CL and encap doxorubicin CL (R2 = 0.58). Mean ± SD of encap doxorubicin area under the concentration versus time curve (AUC) and TSC splenic outflow were 2.4 ± 0.5 mg/mL·h and 0.5 ± 0.1 s-1, respectively. There was a positive linear relationship between TSC splenic outflow and encap doxorubicin AUC (R2 = 0.85). There was no relationship between TSC AUC in the liver and spleen and PLD PK. Conclusions: These results suggest that TSC is a probe for MPS function and PLD PK and may be used to individualize PLD therapy in pts with EOC and other malignancies. Evaluation of the relationship between TSC and PLD PD is undergoing further investigation.

Repeated ambulatory intrapleural chemotherapy for malignant pleural mesothelioma.

7088 Background: Malignant pleural mesothelioma (MPM) is associated with a poor prognosis and high mortality rate. Multimodal regimens involving extirpative lung or pleural surgery have had limited success and may be ill-suited for many patients. We offer an alternative multimodal lung-sparing treatment regimen for MPM. Methods: This is a single institution review of 25 patients with advanced MPM who underwent thoracoscopic intrapleural (IP) port placement and were treated with repeated, ambulatory IP chemotherapy (cisplatin and doxorubin). Select patients received concurrent IV pemetrexed and cisplatin or carboplatin. After 8 weeks the pleural space was imaged with radioactive technetium-labeled sulfur colloid. If the distribution was uniform, patients were given 15 mCi IP P-32. Following treatment, catheters were removed, and pleural surfaces were inspected and biopsied by video thoracoscopy. Select patients with progressive disease underwent additional surgery. Statistical analysis was done using Stata/IC 11.0 (Stata Corporation, College Station, Texas). Results: Twenty-five adult patients (20 male, median age 70, range 45-80) underwent ambulatory IP chemotherapy. Eight patients had pleural and peritoneal involvement. Few complications were attributed to IP chemotherapy. Median overall survival time was 12 months (interquartile range 7.7-20.1). Thirteen patients received concurrent IV chemotherapy. This subgroup had an improved median survival of 16.3 months (range 1.3-49.5) vs 10.5 months (5.7-31.8) without IV chemotherapy (p=0.83). Seven patients received IP P-32 radiotherapy. This did not appear to affect survival. Nine patients underwent additional surgery (3 extrapleural pneumonectomy and 6 pleurectomy/ decortication); this did not appear to affect survival (p=0.14). Conclusions: A multimodal approach including repeated IP chemotherapy, IV chemotherapy, and IP radiation is a feasible, safe alternative for select patients with advanced MPM, including those with multicavity disease. This regimen did not prevent patients from undergoing subsequent surgical procedures. More patients are needed to better power subgroups for analysis, improve selection criteria, and optimize treatment.

Nonmelanoma Skin Cancer

Nonmelanoma Skin Cancer

Evaluation of Sentinel Lymph Node Biopsy in Clinically Node-Negative Breast Cancer

In patients with clinically node-negative breast cancer, diagnosed with palpation and several types of imaging examination, sentinel lymph nodes accurately predict the status of the other axillary nodes, which determine the nature of subsequent adjuvant treatment. In addition, compared with axillary lymph node dissection, sentinel-node biopsy results in less postoperative morbidity, including pain, numbness, swelling, and reduced mobility in the ipsilateral arm. We analyzed the validity of the sentinel node biopsy procedure using dual-agent injection of blue dye and radioactive colloid performed in our hospital from May 2006 through March 2010. A total of 258 breasts of 253 patients were studied. Simultaneous axillary lymph node dissection was performed only if rapid intraoperative diagnosis identified metastasis in sentinel lymph nodes. The identification rate, accuracy, provisional false-negative rate, which was calculated with data from all 65 patients whose sentinel lymph nodes had metastasis, and axillary recurrence rate of sentinel node biopsy were calculated. The sentinel node identification rate was 99.2%, and the accuracy of sentinel lymph node status was 98.0%. The provisional false-negative rate was 7.7%. During an observation period averaging 24 months, axillary recurrence was observed in only 1 of 256 cases (0.4%), and there were no cases of parasternal recurrence. In patients who underwent sentinel-node biopsy without axillary lymph node dissection, there was no obvious morbidity. Our sentinel-node biopsy procedure yielded satisfactory results, which were not inferior to the results of previous clinical trials. Thus, we conclude our sentinel-node biopsy procedure is feasible. If the efficacy and safety of sentinel-node biopsy are confirmed in several large-scale randomized controlled trials in Europe and the United States, sentinel-node biopsy will become a standard surgical technique in the management of clinically node-negative breast cancer.

Multispectral Real-time Fluorescence Imaging for Intraoperative Detection of the Sentinel Lymph Node in Gynecologic Oncology

The prognosis in virtually all solid tumors depends on the presence or absence of lymph node metastases.1-3 Surgical treatment most often combines radical excision of the tumor with a full lymphadenectomy in the drainage area of the tumor. However, removal of lymph nodes is associated with increased morbidity due to infection, wound breakdown and lymphedema.4,5 As an alternative, the sentinel lymph node procedure (SLN) was developed several decades ago to detect the first draining lymph node from the tumor.6 In case of lymphogenic dissemination, the SLN is the first lymph node that is affected (Figure 1). Hence, if the SLN does not contain metastases, downstream lymph nodes will also be free from tumor metastases and need not to be removed. The SLN procedure is part of the treatment for many tumor types, like breast cancer and melanoma, but also for cancer of the vulva and cervix.7 The current standard methodology for SLN-detection is by peritumoral injection of radiocolloid one day prior to surgery, and a colored dye intraoperatively. Disadvantages of the procedure in cervical and vulvar cancer are multiple injections in the genital area, leading to increased psychological distress for the patient, and the use of radioactive colloid.Multispectral fluorescence imaging is an emerging imaging modality that can be applied intraoperatively without the need for injection of radiocolloid. For intraoperative fluorescence imaging, two components are needed: a fluorescent agent and a quantitative optical system for intraoperative imaging. As a fluorophore we have used indocyanine green (ICG). ICG has been used for many decades to assess cardiac function, cerebral perfusion and liver perfusion.8 It is an inert drug with a safe pharmaco-biological profile. When excited at around 750 nm, it emits light in the near-infrared spectrum around 800 nm. A custom-made multispectral fluorescence imaging camera system was used.9.The aim of this video article is to demonstrate the detection of the SLN using intraoperative fluorescence imaging in patients with cervical and vulvar cancer. Fluorescence imaging is used in conjunction with the standard procedure, consisting of radiocolloid and a blue dye. In the future, intraoperative fluorescence imaging might replace the current method and is also easily transferable to other indications like breast cancer and melanoma.

Multispectral Real-time Fluorescence Imaging for Intraoperative Detection of the Sentinel Lymph Node in Gynecologic Oncology

The prognosis in virtually all solid tumors depends on the presence or absence of lymph node metastases.1-3 Surgical treatment most often combines radical excision of the tumor with a full lymphadenectomy in the drainage area of the tumor. However, removal of lymph nodes is associated with increased morbidity due to infection, wound breakdown and lymphedema.4,5 As an alternative, the sentinel lymph node procedure (SLN) was developed several decades ago to detect the first draining lymph node from the tumor.6 In case of lymphogenic dissemination, the SLN is the first lymph node that is affected (Figure 1). Hence, if the SLN does not contain metastases, downstream lymph nodes will also be free from tumor metastases and need not to be removed. The SLN procedure is part of the treatment for many tumor types, like breast cancer and melanoma, but also for cancer of the vulva and cervix.7 The current standard methodology for SLN-detection is by peritumoral injection of radiocolloid one day prior to surgery, and a colored dye intraoperatively. Disadvantages of the procedure in cervical and vulvar cancer are multiple injections in the genital area, leading to increased psychological distress for the patient, and the use of radioactive colloid. Multispectral fluorescence imaging is an emerging imaging modality that can be applied intraoperatively without the need for injection of radiocolloid. For intraoperative fluorescence imaging, two components are needed: a fluorescent agent and a quantitative optical system for intraoperative imaging. As a fluorophore we have used indocyanine green (ICG). ICG has been used for many decades to assess cardiac function, cerebral perfusion and liver perfusion.8 It is an inert drug with a safe pharmaco-biological profile. When excited at around 750 nm, it emits light in the near-infrared spectrum around 800 nm. A custom-made multispectral fluorescence imaging camera system was used.9. The aim of this video article is to demonstrate the detection of the SLN using intraoperative fluorescence imaging in patients with cervical and vulvar cancer. Fluorescence imaging is used in conjunction with the standard procedure, consisting of radiocolloid and a blue dye. In the future, intraoperative fluorescence imaging might replace the current method and is also easily transferable to other indications like breast cancer and melanoma.