Sentinel Lymph Node Mapping in Lung Cancer: A Pilot Study for the Detection of Micrometastases in Stage I Non-Small Cell Lung Cancer.

Lymphadenectomy represents a fundamental step in the staging and treatment of non-small cell lung cancer (NSCLC). To date, the extension of lymphadenectomy in early-stage NSCLC is a debated topic due to its possible complications. The detection of sentinel lymph nodes (SLNs) is a strategy that can improve the selection of patients in which a more extended lymphadenectomy is necessary. This pilot study aimed to refine lymph nodal staging in early-stage NSCLC patients who underwent robotic lung resection through the application of innovative intraoperative sentinel lymph node (SLN) identification and the pathological evaluation using one-step nucleic acid amplification (OSNA). Clinical N0 NSCLC patients planning to undergo robotic lung resection were selected. The day before surgery, all patients underwent radionuclide computed tomography (CT)-guided marking of the primary lung lesion and subsequently Single Photon Emission Computed Tomography (SPECT) to identify tracer migration and, consequently, the area with higher radioactivity. On the day of surgery, the lymph nodal radioactivity was detected intraoperatively using a gamma camera. SLN was defined as the lymph node with the highest numerical value of radioactivity. The OSNA amplification, detecting the mRNA of CK19, was used for the detection of nodal metastases in the lymph nodes, including SLN. From March to July 2021, a total of 8 patients (3 female; 5 male), with a mean age of 66 years (range 48-77), were enrolled in the study. No complications relating to the CT-guided marking or preoperative SPECT were found. An average of 5.3 lymph nodal stations were examined (range 2-8). N2 positivity was found in 3 out of 8 patients (37.5%). Consequently, pathological examination of lymph nodes with OSNA resulted in three upstages from the clinical IB stage to pathological IIIA stage. Moreover, in 1 patient (18%) with nodal upstaging, a positive node was intraoperatively identified as SLN. Comparing this protocol to the usual practice, no difference was found in terms of the operating time, conversion rate, and complication rate. Our preliminary experience suggests that sentinel lymph node detection, in association with the accurate pathological staging of cN0 patients achieved using OSNA, is safe and effective in the identification of metastasis, which is usually undetected by standard diagnostic methods.

Management of the axilla in breast cancer patients: critical review, regional modified Delphi consensus and implementation in the Tuscan breast network.

PURPOSE: Data from recently trials have provided practice-changing recommendations in management of the axilla in early breast cancer (eBC). However, further controversies have been raised, resulting in heterogeneous diffusion of these recommendations. Our purpose was to obtain a better homogeneity. MATERIAL AND METHODS: In 2021, the Tuscan Breast Network (TBN) established a consensus with the aim to update recommendations in this area. We performed a literature review on axillary management in eBC patients which led to an expert Delphi consensus aiming to explore the gray areas, build consensus and propose evidence-based suggestions for an appropriate management. Thereafter, we investigate their implementation in clinical practice. RESULTS: (1) DCIS patients should have SLN biopsy only in case of mastectomy or in conservative surgery if tumor is in a location that would preclude future nodal sampling or in case of a mass; (2) ALND may be omitted for 1-2 positive SLN patients undergoing BCS in T1-2 tumors with 1-2 SLN positive, eligible for whole-breast irradiation and adjuvant systemic therapies; (3) consider the option of RNI in patients with 1-3 positive lymph nodes and one or more high-risk characteristics; (4) the population identified in 2) should NOT undergo lymph node irradiation as an alternative to axillary surgery and (5) patients with clinically (pre-operatively) positive axilla, or undergoing primary systemic therapy, or outside the criteria reported in 2) must receive additional ALND and/or RT as per local policy. CONCLUSION: This consensus provided a practical tool to stimulate local and national breast surgical and radiotherapy protocols.

Intraoperative Radioguided Localization of an Occult Neuroendocrine Tumor of the Ileum.

ABSTRACT: We report the intraoperative radioguided localization of an occult well-differentiated neuroendocrine tumor of the ileum in a patient with a known neuroendocrine lymphonodal metastasis in the mesentery. Preoperative imaging included CT, PET/CT with 68 Ga-DOTATOC, and SPECT/CT with 99m Tc-HYNICTOC. These scans revealed morphological and functional properties of the primary tumor localized in the ileum. The day after IV 99m Tc-HYNICTOC injection, the patient underwent surgery, and the target lesion was intraoperatively detected by a collimated handheld γ-probe. Postoperative pathology examination confirmed the target lesion to be a neuroendocrine tumor of the ileum.

Correlation between 18F-FDG PET/CT and diffusion-weighted MRI parameters in head and neck squamous cell carcinoma at baseline and after chemo-radiotherapy. A retrospective single institutional study.

OBJECTIVES: The relationship between glucose metabolism and tumor cellularity before chemo-radiotherapy in patients with head and neck squamous cell carcinoma (SCC) has never been compared with that of patients evaluated after treatment. This retrospective study analyzed the correlation between glucose metabolism parameters expressed by standardized uptake value (SUV) derived from 18F-fluorodeoxyglucose (18F-FDG) PET/CT and cellularity tumor parameters expressed by apparent diffusion coefficients (ADC) derived from diffusion-weighted (DW) MRI in untreated and treated patients with head and neck SCC. METHODS: In 19 patients with no previous exposure to any treatment and 17 different chemo-radiotreated patients with head and neck SCC, we correlated the semi-quantitative uptake values (SUVmax, SUVpeak, and SUVmean) with the ADC functional parameters (ADCmin, ADCmean) including the standard deviation of ADC values (ADCsd). RESULTS: No significant correlation was found between glucose metabolism parameters and ADCmin or ADCmean in untreated and treated patient groups. However, in untreated patients, significant inverse correlations were found between ADCsd and SUVmax (P = 0.039, r = -0.476), SUVpeak (P = 0.003, r = -0.652) and SUVmean (P = 0.039, r = -0.477). Analyses after chemo-radiotherapy in 17 patients showed no significant correlation between glucose metabolism parameters and DW MRI values, excluding a persistent significant (but lower intensity) inverse correlation between SUVpeak and ADCsd (P = 0.033, r = -0.519). CONCLUSIONS: The demonstrated relationships suggest complex interactions especially between metabolic activity and heterogeneity of tumoral tissue, which might play a complementary role in the assessment of head and neck SCC. TRIAL DATE OF REGISTRATION AND REGISTRATION NUMBER: Our retrospective study was registered on April 9th, 2020 by the Ethics Committee of the Coordinating Center "Area Vasta Nord Ovest" (CEAVNO) with Registration Number CEAVNO09042020.

Have Volume-based Parameters of Positron Emission Tomography/Computed Tomography Prognostic Relevance for Patients With Potentially Platinum-responsive Recurrent Ovarian Cancer? A Single Center Italian Study.

BACKGROUND/AIM: To assess the prognostic relevance of volume-based parameters [whole body (wb)-metabolic tumor volume (MTV) and wb-total lesion glycolysis (TLG)] of pretreatment PET/CT in patients with potentially platinum-responsive recurrent ovarian cancer. PATIENTS AND METHODS: This retrospective investigation analyzed 67 patients at first relapse. RESULTS: At univariate analysis, post-relapse survival and overall survival correlated with residual disease after primary surgery (RD) (p=0.015 and 0.049, respectively), time to recurrence (p=0.005 and p=0.0003), number of recurrence sites (p=0.001 and p=0.0005), treatment at recurrence (p=0.044 and 0.043) and wb-MTV (p=0.023 and 0.021) but not with wb-TLG. RD, time to recurrence and number of recurrence sites, but not wb-MTV, were independent prognostic variables for post-relapse survival, and time to recurrence and number of recurrence sites, but not wb-MTV, were independent prognostic factors for overall survival. CONCLUSION: Volume-based parameters of PET/CT are not independent predictors of clinical outcome in potentially platinum-responsive recurrent ovarian cancer.

Novel Experience in Hybrid Tracers: Clinical Evaluation of Feasibility and Efficacy in Using ICG-99mTc Nanotop for Sentinel Node Procedure in Breast Cancer Patients.

PURPOSE: The clinical introduction of a radioactive and fluorescent hybrid tracer allowed for preoperative lymphatic mapping and intraoperative real-time fluorescence tracing of the sentinel lymph node (SLN) by a single injection. The aim of this feasibility study is to evaluate the first-in-human use of the hybrid tracer by combining indocyanine green (ICG) and radiocolloid based on Nanotop compound (99mTc Nanotop) for SLN biopsy (SLNB) in breast cancer patients. METHODS: The day before surgery, ICG-99mTc Nanotop was injected periareolarly in breast cancer patients scheduled for SLNB. Planar lymphoscintigraphic (PL) and SPECT/CT images were then acquired. An intraoperative optonuclear probe was used to detect SLN gamma and fluorescent signals. The harvested SLNs were examined by hematoxylin-eosin staining, and patients were clinically evaluated 1 month after surgery. RESULTS: Twenty-one consecutive patients were enrolled. The PL and SPECT/CT techniques identified at least 1 SLN in all patients for a preoperative sentinel detection rate of 100%. SPECT/CT revealed 3 additional lymph nodes in the same nodal basin, which had not been visualized on conventional PL (κ = 0.747; P < 0.005). All 30 preoperative SLNs were localized and excised up to 16 hours after injection. The counts measured via gamma tracing showed a very strong correlation with those measured via near-infrared fluorescent tracing (P < 0.005, r = 0.964). No adverse reactions were observed. CONCLUSIONS: The SLNB technique used with the ICG-99mTc Nanotop tracer resulted to be feasible, reliable, and safe. This hybrid compound allowed us to obtain excellent performance in terms of both preoperative lymphatic mapping and intraoperative SLN detection in breast cancer patients.

Comparison of 99mTc-Labeled Colloid SPECT/CT and Planar Lymphoscintigraphy in Sentinel Lymph Node Detection in Patients with Melanoma: A Meta-Analysis.

We compared the detection rate (DR) for sentinel lymph nodes (SLN), the number of SLNs and the subjects with additional SLNs of single-photon emission computed tomography (SPECT/CT) and planar lymphoscintigraphy (PL) in patients with melanoma. Furthermore, we evaluated the impact of SPECT/CT on surgical plans. Articles containing head-to-head comparisons between SPECT/CT and PL were searched in Pubmed/MEDLINE and Scopus. The literature search was updated until December 31st, 2019. DR was calculated on a per patient-based analysis; the studies were pooled by their odds ratios (ORs) with a random effects model to assess the significance of difference (p < 0.05). The number of additional SLNs (calculated as the relative risk) and pooled proportion of patients with additional SLNs were investigated. The pooled ratio of surgical procedures influenced by the SPECT/CT findings was calculated. Seventeen studies with 1438 patients were eligible for the calculation of DR of SPECT/CT and PL. The average DR was 98.28% (95% confidence interval (95% CI): 97.94-99.19%) for the SPECT/CT and 95.53% (95% CI: 92.55-97.77%) for the PL; OR of 2.31 (95% CI: 1.66-4.18, p < 0.001) in favor of the SPECT/CT. There was a relative risk of a higher number of SLNs (1.13) for the SPECT/CT and 17.87% of patients with additional SLNs were detected by SPECT/CT. The average impact of SPECT/CT on surgery resulted in 37.43% of cases. This meta-analysis favored SPECT/CT over PL for the identification of SLNs in patients with melanoma due to a higher DR, reproducibility, number of SLNs depicted, proportion of patients with additional SLNs and the impact on the surgical plan. However, PL remains a good option due to the high values of the DR for SLNs.

Radioguided Surgery, a Cost-Effective Strategy for Treating Solitary Pulmonary Nodules: 20-Year Experience of a Single Center.

INTRODUCTION: Surgical resection with minimally invasive approach is the gold standard for both definitive diagnosis and treatment of solitary pulmonary nodules (SPNs); however, it can be difficult to pinpoint small, deep, or subsolid nodes without palpating lung parenchyma. The primary endpoint of this study is showing that radioguided surgery is a cost-effective strategy to improve the effectiveness of video-thoracoscopic localization/resection of SPNs/ground-glass opacities (GGOs). Secondary endpoints are analyzing the morbidity of this technique and tips and tricks to better manage this method. METHODS: SPN smaller than 20 mm and/or with a distance from the visceral pleura ≥5 mm underwent minimally invasive resection after computed tomography-guided injection of a solution composed of 0.1/0.2 mL of 99Tc-labeled human serum albumin microspheres and 0.1 mL of nonionic contrast. In the operating theater, a collimated probe connected to a gamma ray detector allowed localization of the target area. RESULTS: Between 1997 and 2018, a total of 451 patients with SPN/GGO underwent minimally invasive surgery with a radioguided technique at our hospital. The mean SPN diameter was 13 mm (range, 5-20 mm), and the mean distance from the visceral pleura was 15 mm (range, 6-29 mm). The mean time to a localizing nodule was 3 minutes (range, 1-5 minutes). No significant injection-related complications were reported; only 3.3% of patients (15 of 451) developed pneumothorax. Both 30- to 60-day and 90-day mortality were 0%. The rate of postoperative complications was 2.53% (prolonged air leak). The conversion rate to thoracotomy was 1.55% (7 of 451). CONCLUSIONS: Our 20-year experience shows that radioguided thoracoscopic surgery is a safe and feasible strategy to treat suspicious SPN/GGO, with a success rate of 98%.

Positron Emission Tomography/Computed Tomography in Platinum-sensitive Recurrent Ovarian Cancer: A Single-center Italian Study.

AIM: To assess the correlation between contrast-enhanced computed tomography (CE-CT) and positron-emission tomography (PET)/CT results and surgical and pathological findings in patients with recurrent platinum-sensitive ovarian cancer who underwent secondary cytoreduction. PATIENTS AND METHODS: 18F-fluorodeoxyglucose (18F-FDG) PET/CT with/without CE-CT were performed before 56 cytoreductive surgeries in 49 patients with suspicious recurrent ovarian cancer. RESULTS: 18F-FDG PET/CT showed higher sensitivity and diagnostic accuracy compared with CE-CT for both the whole series (100% versus 90.6%, respectively, and 97.8% versus 85.3%), and the 24 cases in which both examinations were performed (100% versus 87.0% and, respectively, 95.8% versus 83.3%). The addition of CE-CT to 18F-FDG PET/CT did not improve its diagnostic reliability. CONCLUSION: 18F-FDG PET/CT appears to be the more reliable imaging technique for the evaluation of patients with suspicious recurrent ovarian cancer, and for the selection of those more suitable for secondary cytoreductive surgery.

The sentinel lymph node biopsy technique in papillary thyroid carcinoma: The issue of false-negative findings.

BACKGROUND: The management of papillary thyroid carcinoma (PTC) is changed after introduction of sentinel lymph node biopsy (SNB) technique for nodal staging. Some debate still surrounds the accuracy of this procedure in terms of wide heterogeneity of sentinel lymph node detection and false-negative findings. AIM: to identify the key issues which make it difficult the usefulness of SNB in PTC. METHODS: A comprehensive computer literature search of meta-analyses published in PubMed/MEDLINE and Cochrane library database until June 30, 2019 was conducted. We used a search algorithm based on this combination of terms: (i) "thyroid neoplasm" or "thyroid cancer" or "thyroid carcinoma" or "thyroid malignancy" or "meta-analysis" or "systematic review") AND (ii) "sentinel lymph node biopsy". RESULTS: Comparing 4 written meta-analyses published in the literature, the diagnostic performance of SNB technique in PTC has been summarized. Relatively high false-negative rates (FNR) were reported for each SNB methods: vital-dye (VD: 12.7%; 7%; 0-38%), 99mTc-nanocolloid planar lymphoscintigraphy with the use of intraoperative hand-held gamma probes (LS: 11.3%; 16%; 0-40%), combined LS with VD (LS+VD: 0%; 0-17%), LS with the additional contribution of preoperative SPECT/CT (7-8%). CONCLUSION: Evidence-based data about the diagnostic performance of SNB in PTC are increasing. The nuclear medicine community should reach a consensus on the operational definition of the SLN to better guide the surgeon in identifying the lymph nodes most likely contain metastatic cells. Standardization of SLN identification, removal and analysis are required.

Lymphoscintigraphy and sentinel lymph node biopsy in vulvar carcinoma: update from a European expert panel.

PURPOSE: This study aimed to update the clinical practice applications and technical procedures of sentinel lymph node (SLN) biopsy in vulvar cancer from European experts. METHODS: A systematic data search using PubMed/MEDLINE database was performed up to May 29, 2019. Only original studies focused on SLN biopsy in vulvar cancer, published in the English language and with a minimum of nine patients were selected. RESULTS: Among 280 citations, 65 studies fulfilled the inclusion criteria. On the basis of the published evidences and consensus of European experts, this study provides an updated overview on clinical applications and technical procedures of SLN biopsy in vulvar cancer. CONCLUSIONS: SLN biopsy is nowadays the standard treatment for well-selected women with clinically negative lymph nodes. Negative SLN is associated with a low groin recurrence rate and a good 5-year disease-specific survival rate. SLN biopsy is the most cost-effective approach than lymphadenectomy in early-stage vulvar cancer. However, future trials should focus on the safe extension of the indication of SLN biopsy in vulvar cancer. Although radiotracers and optical agents are widely used in the clinical routine, there is an increasing interest for hybrid tracers like indocyanine-99mTc-nanocolloid. Finally, it is essential to standardise the acquisition protocol including SPECT/CT images, and due to the low incidence of this type of malignancy to centralise this procedure in experienced centres for personalised approach.

Detection of Uterine Leiomyosarcoma Peritoneal Lesions by SPECT/CT and ROLL Technique.

We reported the preoperative radio-guided localization of 4 peritoneal metastatic nodules in the case of a 45-year-old woman with uterine leiomyosarcoma. Three lines of chemotherapy were tried, but cardiotoxicity occurred. Within the context of so-called GOSTT (guided intraoperative scintigraphic tumor targeting), preoperative radio-guided localization of peritoneal metastases enabled their subsequent radio-guided excisional biopsy. SPECT/CT allowed for anatomical localization of the hot lesions and generated a 3-dimensional volume-rendering roadmap, facilitating a surgical approach.

Lymphoscintigraphy for the evaluation of limb lymphatic flow disorders: Report of technical procedural standards from an Italian Nuclear Medicine expert panel. / Linfogammagrafía para la evaluación de trastornos del flujo linfático de las extremidades: informe de estándares de procedimientos técnicos de un panel de expertos de medicina nuclear italiano.

Lymphoscintigraphy represents the "gold standard" for diagnosis of lymphedema, but an important limitation is the lack of procedural standardization. The aim of this Italian expert panel was to provide a procedural standard for lymphoscintigraphy in the evaluation of lymphatic system disorders. Topic anaesthetic gels containing lidocaine should be avoided. Patients should remove compressive dressings. Total recommended activity for 99mTc-nanocolloid administration in adults is 74MBq, or 37MBq per limb and per investigated compartment, in single or multiple aliquots. 2-3 subcutaneous injections should be performed (II-III±I interdigital space of each hand/foot), avoiding intravascular injection. Deep lymphatic system of lower limbs should be evaluated in presence of dermal back-flow or lymphatic stasis (1-2 subfascial administrations in retro-malleolar or plantar region). Planar images should be acquired from injection site to liver with whole-body or serial static acquisitions 20' and 90' after subcutaneous administration. Additional information on lymphatic pathways is obtained after a quick and/or prolonged exercise protocol. SPECT/CT is recommended to study the thoracic, abdominal and pelvic territories. When required, deep lymphatic system of lower limbs should be evaluated with static acquisition 90' after subfascial administration. The report should describe administration and imaging procedure, exercise protocol, qualitative and semi-quantitative analysis (wash-out rate, transport index), potential sources of error. Due to the essential role fulfilled by lymphoscintigraphy in clinical management of primary and secondary lymphedema, an effort for the standardization of this technique should be made to provide the clinicians with a homogeneous and reliable technical methodology.

Effect of Sentinel Node Biopsy in Clinically N0, BRAF V600E-Mutated, Small Papillary Thyroid Carcinoma: A Pilot Study.

PURPOSE: BRAF V600E mutation papillary thyroid cancer (PTC) is more aggressive with a higher risk of lymph node involvement and a poorer prognosis. Prior studies failed to demonstrate the superiority of prophylactic lymphadenectomy. We investigated the utility of additional radio-guided sentinel node biopsy (SNB). METHODS: We analyzed 15 patients with N0 PTC by ultrasound and BRAF mutation on preoperative biopsy treated with total thyroidectomy (TT) or TT + prophylactic central neck dissection (PCND) alone or with SNB. Conventional surgery was performed before SNB. We recorded primary tumor diameter, multifocality, extrathyroid infiltration, neoplastic emboli, and tall cell variant. At follow-up, we evaluated basal and stimulated thyroglobulin and ultrasound or radioiodine scintigraphy. RESULTS: Of 15 consecutive patients, 5 received conventional surgery alone, and 10 had SNB. For the first group, 4 underwent TT, and 1 had TT + PCND. Among the SNB group, 1 had no sentinel node detected and underwent a simple TT, 2 had TT + PCND+ SNB in the lateral compartment, and 7 had TT + SNB in 1 to 3 neck compartments. Micrometastases were found in 1 of 3 PCND specimens. Sentinel node biopsy revealed metastasis in 3 of 6 central compartment biopsies, in 2 of 6 biopsies in the ipsilateral lateral compartment, and in none of 2 biopsies in the contralateral compartment. Sentinel node biopsy allowed the removal of micrometastases in 4 of 10 patients. At 53 months' (mean) follow-up, no relapse was documented. CONCLUSIONS: Radio-guided SNB correctly and efficiently stages cN0 BRAF-mutated PTC patients. Sentinel node biopsy could limit time-consuming, risk-exposing compartmental prophylactic dissections.

Sentinel Lymph Node Biopsy in Small Papillary Thyroid Cancer: A Meta-analysis.

PURPOSE: The aim of this study was to compare reported results on available techniques for sentinel lymph node detection rate (SDR) in papillary thyroid cancer (PTC). METHODS: The MEDLINE database was searched via a PubMed interface to identify original articles regarding sentinel lymph node biopsy (SNB) in thyroid cancer. Studies were stratified according to the sentinel lymph node (SLN) detection technique: vital-dye (VD), Tc-nanocolloid planar lymphoscintigraphy with the use of intraoperative hand-held gamma probes (LS), both Tc-nanocolloid planar lymphoscintigraphy with intraoperative use of hand-held gamma probe and VD (LS + VD), Tc-nanocolloid planar lymphoscintigraphy with the additional contribution of preoperative SPECT/CT, and intraoperative use of hand-held gamma probe (LS-SPECT/CT). Pooled SDR values were presented with a 95% confidence interval (CI) for each SLN detection techniques. A Z-test was used to compare pooled SDR estimates. False-negative rates were summarized for each method. RESULTS: Forty-five studies were included. Overall SDRs for the VD, LS, LS + VD, and LS-SPECT/CT techniques were 83% (95% CI, 77%-88%; I = 78%), 96% (95% CI, 90%-98%; I = 68%), 87% (95% CI, 65%-96%; I = 75%), and 93% (95% CI, 86%-97%; I = 0%), respectively. False-negative rates were 0% to 38%, 0% to 40%, 0% to 17%, and 7% to 8%, respectively. CONCLUSIONS: In patients with PTC, Tc-nanocolloids offer a higher SDR than that of the VD technique. The addition of SPECT/CT improved identification of metastatic SLNs outside the central neck compartment.

Sentinel lymph node biopsy in small papillary thyroid cancer. A review on novel surgical techniques.

PURPOSE: Sentinel lymph node biopsy (SNB) in patients with papillary thyroid carcinoma (PTC) and negative for clinically neck lymph node metastatic involvement (N0) has emerged as a promising minimally invasive procedure to detect metastatic nodes. METHODS: The MEDLINE database was searched via the PubMed interface on 10 January 2018 for the MeSH headings "sentinel lymph node biopsy" and "thyroid carcinoma". RESULTS: Vital blue dye, radioisotope, and the combination of both techniques are used in PTC patients. These methods and the emerging role of SPECT/CT are discussed in this review. The sentinel lymph node (SLN) identification rates ranged from 0 to 100% for blue dye, 83 to 100% for radioisotopes, and 66 to 100% for the combination of both techniques, respectively. CONCLUSIONS: SNB based on radioisotope technique with the use of intraoperative gamma-probe is an accurate and safe method that allows the highest SLN detection rate. There is sufficient evidence to propagate the increasing use of SNB procedure that has the potential to avoid prophylactic lymph node surgery in patients clinically N0.

Clinical Impact of Radioguided Localization in the Treatment of Solitary Pulmonary Nodule: A 20-Year Retrospective Analysis.

PURPOSE: Incidental solitary pulmonary nodules (SPNs) have become an increasingly common CT finding worldwide. Although there are currently many imaging strategies for evaluating SPNs, the differential diagnosis and management of SPNs remains complex because of overlap between benign and malignant processes. Moreover, transbronchial or percutaneous CT-guided biopsies do not always allow definitive diagnoses. In such cases, video-assisted thoracic surgery (VATS) has become the preferred surgical procedure for diagnosis and, in selected cases, for treatment of indeterminate SPNs. The difficulties in localizing smaller, deeper, and ground-glass nodules have been approached with different techniques. The aim of this study was to report 20 years of experience with radioguided thoracoscopic resection of SPNs at the Regional Centre of Nuclear Medicine of Pisa. METHODS: Three hundred ninety-five patients with SPNs less than 2 cm and deeper than 5 mm below the visceral pleura underwent CT-guided injection of a suspension composed of 0.1 to 0.2 mL Tc-labeled human albumin macroaggregates (Tc-MAA) and of 0.2 to 0.3 mL of nonionic contrast medium into or adjacent to the SPN. During VATS, the pulmonary area with the highest target/background ratio identified by an 11-mm-diameter collimated thoracoscopic gamma probe was resected. RESULTS: From 1997 to 2016, approximately 395 patients with SPN underwent VATS wedge resection using the radioguided technique. Mean SPN size was 13 mm (range, 5-20 mm) with mean distance of 15 mm (range, 6-39 mm) from the visceral pleura. Mean VATS procedural time was 40 minutes (range, 20-90 minutes), with an average time of 3 minutes (range, 1-5 minutes) to localize the nodule. Neither mortality nor major perioperative complication was reported. The success rate of VATS with radioguidance in our series was 99%. Histological examination revealed 206 benign lesions (52%), 59 primary lung tumors (15%), and 130 metastatic nodules (33%). CONCLUSIONS: This study demonstrates that radioguided SPN localization by VATS is a feasible, safe, and rapid procedure with highly successful rate of SPN resection.

Association between semiquantitative PET parameters and molecular subtypes of breast invasive ductal carcinoma.

BACKGROUND: Molecular subtypes of breast cancer have been proposed since 2012. The correlation between various baseline [18F]fluorodeoxyglucose ([18F]FDG) uptake parameters, including total lesion glycolysis (TLG), and molecular subtypes of primary breast cancer lesions in patients with invasive ductal cancer will be investigated. METHODS: Staging [18F]FDG PET/CT for breast invasive ductal carcinoma were retrospectively evaluated. Breast lesions were examined for estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and proliferation index (Ki-67). Breast tumors were classified into five molecular subtypes: Luminal A, Luminal B-HER2(-), Luminal B-HER2(+), HER2(+) and Basal or Triple Negative cancers. The correlations between tumor characteristics and PET semiquantitative data of primary breast lesion (SUVmean, SUVmax, Mean tumor volume (MTV), TLG) were assessed. Specific Breast Uptake Ratio (SBUR) is used as a new quantification method of breast uptake to correct for physiological background activity. RESULTS: Fifty-eight patients were included. TLG was significantly higher in triple negative group when compared with luminal A (P<0.01). Significantly higher uptake was found in triple negative lesions when compared with luminal B-HER2(-) and luminal B-HER2(+) categories using SUVmax, SUVmean and TLG (all P<0.05). Conversely, no statistically significant difference for [18F]FDG uptake was observed between all other molecular subtypes. No value of SBUR in terms of correlation with histopathological parameters was demonstrated. CONCLUSIONS: TLG was superior to SUVmax and SUVmean in differentiating between triple negative breast cancer lesions and all other molecular subtypes. SBUR was not different statistically between various molecular subtypes.

Radioguided Occult Lesion Localization: Technical Procedures and Clinical Applications.

PURPOSE: Regarding radioguided surgery, the concept of "radioguided occult lesion localization" (ROLL) is based on both preoperative interventional imaging and intraoperative radioguided detection of a clinically occult neoplastic lesion. METHODS: This methodology consists in the direct administration into the lesion of Tc-macroaggregated human albumin formed by relatively large particles retained at the injection site, which direct radioguided excisional biopsy. RESULTS: This modality has expanded from the classic application of ROLL for nonpalpable breast lesions to other tumors, such as solitary pulmonary nodules or recurrences from differentiated thyroid carcinoma. In 2011, in order to improve the classification of different radioguided surgical procedures, ROLL applications were included in the more complete concept of GOSTT (Guided intraOperative Scintigraphic Tumor Targeting). This concept was introduced to include the entire range of basic and advanced radioguided procedures necessary to supply a "road map" for the surgeon. CONCLUSIONS: The terms ROLL and GOSTT have further developed by incorporating novel modalities such as hybrid tracers for simultaneous fluorescence and radioactive signal detection and innovative navigation systems based on mixed-reality protocols.

Advances in radioguided surgery in oncology.

The sentinel lymph node (SLN) biopsy is probably the most well-known radioguided technique in surgical oncology. Today SLN biopsy reduces the morbidity associated with lymphadenectomy and increases the identification rate of occult lymphatic metastases by offering the pathologist the lymph nodes with the highest probability of containing metastatic cells. These advantages may result in a change in clinical management both in melanoma and breast cancer patients. The SLN evaluation by pathology currently implies tumor burden stratification for further prognostic information. The concept of SLN biopsy includes pre-surgical lymphoscintigraphy as a "roadmap" to guide the surgeon toward the SLNs and to localize unpredictable lymphatic drainage patterns. In addition to planar images, SPECT/CT improves SLN detection, especially in sites closer to the injection site, providing anatomic landmarks which are helpful in localizing SLNs in difficult to interpret studies. The use of intraoperative imaging devices allows a better surgical approach and SLN localization. Several studies report the value of such devices for excision of additional sentinel nodes and for monitoring the whole procedure. The combination of preoperative imaging and radioguided localization constitutes the basis for a whole spectrum of basic and advanced nuclear medicine procedures, which recently have been encompassed under the term "guided intraoperative scintigraphic tumor targeting" (GOSTT). Excepting SLN biopsy, GOSTT includes procedures based on the detection of target lesions with visible uptake of tumor-seeking radiotracers on SPECT/CT or PET/CT enabling their subsequent radioguided excisional biopsy for diagnostic of therapeutic purposes. The incorporation of new PET-tracers into nuclear medicine has reinforced this field delineating new strategies for radioguided excision. In cases with insufficient lesion uptake after systemic radiotracer administration, intralesional injection of a tracer without migration may enable subsequent excision of the targeted tissue. This approach has been helpful in non-palpable breast cancer and in solitary pulmonary nodules. The introduction of allied technologies like fluorescence constitutes a recent advance aimed to refine the search for SLNs and tracer-avid lesions in the operation theatre in combination with radioguidance.