Lutetium [177Lu]-DOTA-TATE in gastroenteropancreatic-neuroendocrine tumours: rationale, design and baseline characteristics of the Italian prospective observational (REAL-LU) study.

PURPOSE: Gastroenteropancreatic -neuroendocrine tumours (GEP-NETs) are commonly treated with surgical resection or long-term therapies for tumour growth control. Lutetium [177Lu]-DOTA-TATE was approved for the treatment of GEP-NETs after the phase III NETTER 1trial demonstrated improved progression free survival, objective response rates and health-related quality of life (HRQoL) compared to high-dose somatostatin analogues. No real-world data exist on prescribing habits and clinically significant endpoints for [177Lu]Lu-DOTA-TATE treatment in Italy. REAL-LU is a multicentre, long-term observational study in patients with unresectable/metastatic GEP-NETs progressing on standard therapies in Italian clinical practice. A pre-specified interim analysis was performed at the end of the enrolment period, data from which are described herein. METHODS: Overall duration of REAL-LU will be approximately 48 months, with 12- and 36-month recruitment and follow-up periods, respectively. The primary objective is to evaluate [177Lu]Lu-DOTA-TATE effectiveness in terms of progression-free survival. Secondary objectives include safety, impact on HRQoL, and identification of prognostic factors. This pre-specified interim analysis describes patient profiles, at the end of enrollment, of those prescribed [177Lu]Lu-DOTA-TATE for GEP-NETs in Italy. RESULTS: Among 161 evaluable patients, mean age was 64.7 ± 10.3 years at study entry, 83.8% presented with no clinical signs of disease at physical examination, and most had minor disease symptoms. All patients had metastatic disease, most commonly in the liver (83.9%) with a median of two metastatic sites. In 90.7% of patients, the disease was stage IV, and 68.3% had ≥ 1 target lesion. [177Lu]Lu-DOTA-TATE was prescribed mainly as second-line therapy (61.6%) and following surgery (58.4%). HRQoL assessments revealed high levels of functioning and low levels of symptoms at baseline; 50.0% of patients were symptom-free at study entry. CONCLUSION: The characteristics of patients who received [177Lu]Lu-DOTA-TATE in Italy are similar to those of the GEP-NET population of NETTER 1 with trial but with a higher proportion of patients with a grade 2 (71%). With regard to the tumor grade profile, our study cohort appears to be closer to that of NETTER-2 study population which included patients with G2 or G3 advanced GEP-NETs (i.e. Ki-67 ≥ 10% and ≤ 55%). Further analysis of effectiveness and safety can be anticipated as REAL-LU data mature. STUDY REGISTRATION: ClinicalTrials.gov, NCT04727723; Study Registration Date: 25 January, 2021; https://clinicaltrials.gov/study/NCT04727723?cond=NCT04727723&rank=1.

Yttrium-90 Radioembolization for Hepatocellular Carcinoma with Portal Vein Invasion: Validation of the Milan Prognostic Score.

The aim of the present study was to retrospectively analyze clinical outcomes of patients with hepatocellular carcinoma (HCC) and portal vein tumor thrombosis (PVTT) treated with yttrium-90 radioembolization stratified by Milan PVTT score according to PVTT extension, tumor burden, and bilirubin levels. Seventy patients were included and classified into good (n = 15; 21.4%), intermediate (n = 33; 47.1%), and dismal (n = 22; 31.4%) prognostic groups. Median overall survival durations were 24.6 mo, 13 mo (hazard ratio = 3.2; 95% confidence interval [CI], 1.2-9.7; P = .016), and 5.9 mo (hazard ratio = 4.1; 95% CI, 1.4-13.4; P = .0096), respectively. The Milan score represents an easy tool to select patients with HCC with PVTT who may benefit from radioembolization.

Comparison between radioiodine therapy and single-session radiofrequency ablation of autonomously functioning thyroid nodules: A retrospective study.

OBJECTIVE: To compare the efficacy of Radioiodine (RI) and Radiofrequency ablation (RFA) in the treatment of autonomously functioning thyroid nodules (AFTNs). End-points: nodule volume reduction (NVR) and thyroid function normalization. DESIGN, PATIENTS AND MEASUREMENTS: Twenty-two patients (2:20 M:F; 51.9 ± 13.9 years) affected by 25 AFTNs, treated by RFA were retrospectively compared with 25 patients (8:17 M:F; 57.2 ± 12.8 years) affected by a single AFTN treated by RI. Both group showed analogous characteristics as to age, gender, toxic/pretoxic phase and pretreatment nodule volume (calculated by the ellipsoid formula). Thyroid hormone levels and autoimmune thyroid profile were assessed before treatment. A fixed RI activity of 555 MBq (15 mCi) was administered. RFA was performed with an 18G, single-tipped electrode, by the "modified moving shot technique." Thyroid hormones were assessed and the nodule post-treatment volume calculated 12 months after treatment. RESULTS: No statistical difference was found between the post-treatment NVR by comparing RI and RFA (P = 0.69). The volume reduction rates were 68.4 ± 28.9% and 76.4 ± 16.9% after RI and RFA, respectively. As to the thyroid function, 5/25 patients developed clinical hypothyroidism after RI. After RFA, all the 22 patients silenced their AFTN and normalized the thyroid hormones. Subclinical hypothyroidism was recorded in two patients after both RI and RFA. Thus, the functional therapeutic success, defined as the restoration of euthyroidism, was achieved in 18/25 (72%) patients treated by RI and in 20/22 (90.9%) treated by RFA. CONCLUSIONS: No statistical difference in NVR was found between RI and RFA. All patients responded to RI but 5/25 were "over-treated" developing hypothyroidism. RFA was effective in all patients with no case of post-treatment clinical hypothyroidism. No radiation exposure and lower risk of post-treatment hypothyroidism might make RFA the favourite option especially for young patients.

Radium 223 dichloride: a multidisciplinary approach to metastatic castration-resistant prostate cancer.

The role of nuclear medicine physicians in the multidisciplinary team for the management of patients with prostate cancer has been restricted because of a lack of available tools. The only drugs approved to relieve pain related to bone metastases were ß-emitting radiopharmaceuticals. These drugs did not prove to prolong survival when used as single agent and resulted associated with important adverse events. This situation has changed with the introduction of radium 223 because of evidence of improved survival in patients, the good safety profile and the opportunity to avoid clonal selection of tumor cells. Cooperation among physicians involved in cancer management will lead to improvements in the treatment of bone metastases due to prostate cancer and is thought to extend to other tumor types.

Role of Transhepatic Arterial Radioembolization in Metastatic Colorectal Cancer.

The liver represents the most frequent location of metastatic disease in colorectal cancer (CRC). In oligometastatic disease, while surgery remains the mainstay of treatment, loco-regional therapies allow to locally control tumor progression and prolong survival. There is consensus in the use of transhepatic arterial radioembolization (TARE) in metastatic CRC chemorefractory patients, with liver-only or liver-dominant disease. Beyond this indication, TARE may be considered in other clinical scenarios, such as in the second-line combined with chemotherapy, as a bridge in between different lines of systemic therapies, and as ablative technique under specific circumstances. This paper outlines the current evidence for TARE in mCRC and presents possible future indications and directions.

Yttrium-90 transarterial radioembolization for liver metastases from medullary thyroid cancer.

Objectives: Liver metastases occur in 45% of patients with advanced metastatic medullary thyroid cancer (MTC). Transarterial radioembolization (TARE) has been proposed to treat liver metastases (LM), especially in neuroendocrine tumors. The aim of this study was to investigate the biochemical (calcitonin and carcino-embryonic antigen) and objective response of liver metastases from MTC to TARE. Methods: TARE is an internal radiotherapy in which microspheres loaded with ß-emitting yttrium-90 (90Y) are delivered into the hepatic arteries that supply blood to LM. Eight patients with progressive multiple LM underwent TARE and were followed prospectively. They were clinically, biochemically and radiologically evaluated at 1, 4, 12 and 18 months after TARE. Results: Two patients were excluded from the analysis due to severe liver injury and death due to extrahepatic disease progression, respectively. One month after TARE, a statistically significant (P = 0.02) reduction of calcitonin was observed in all patients and remained clinically relevant during follow-up; reduction of CEA, although not significant, was found in all patients. Significant reduction of liver tumor mass was observed 1, 4 and 12 months after TARE (P = 0.007, P = 0.004, P = 0.002, respectively). After 1 month, three of six patients showed partial response (PR) and three of six stable disease (SD) according to RECIST 1.1, while five of six patients had a PR and one of six a SD according to mRECIST. The clinical response remained relevant 18 months after TARE. Excluding one patient, all others showed only a slight and transient increase in liver enzymes. Conclusions: TARE is effective in LM treatment of MTC. The absence of severe complications and the good tolerability make TARE a valid therapeutic strategy when liver LM are multiple and progressive.

Current role of 111In-DTPA-octreotide scintigraphy in diagnosis of thymic masses.

AIMS AND BACKGROUND: Thymic tumors (thymomas and thymic carcinomas) represent 50% of all mediastinal tumors. Thymomas usually express high levels of somatostatin receptors, which enable in vivo imaging with 111In-DTPA-octreotide (OctreoScan®). The aim of this study was to further investigate the role of radionuclide techniques in the diagnosis, staging and follow-up of these tumors. METHODS: Eight patients (5 women, 3 men, age range 35-79 years; mean ± SD 56.1 ± 15.8 years) entered the study. In 4 patients, myasthenia gravis was the presenting symptom. 111In-DTPA-octreotide scan was performed within 3 weeks after contrast enhanced CT and/or MRI. Planar and tomographic images were acquired within 24 hours of the injection of 111 MBq OctreoScan. The scintigraphic results were defined in correlation with the histological findings. RESULTS: Histology revealed thymoma in 3 patients, thymic carcinoma in 1, insular carcinoma of presumably thymic origin in 1, thymic carcinoid in 1, and thymic hyperplasia in 2 patients. Two thymomas were at stage I, 1 thymoma and 1 thymic carcinoma at stage II, 1 insular carcinoma of presumably thymic origin at stage IV, and 1 thymic carcinoid at stage IV. OctreoScan consistently accumulated in primary and/or metastatic sites of thymic tumors while no radiotracer uptake was detected in the 2 patients with benign thymic hyperplasia. In 1 patient with a very large mediastinal mass (13 cm in largest diameter) and multiple metastatic deposits in the lungs, OctreoScan scintigraphy showed a large area of pathological uptake in the anterior mediastinum and a small area of focal uptake in the cervical-dorsal region of the right lung corresponding to a lymph node expressing somatostatin receptors. CONCLUSIONS: OctreoScan is avidly taken up by thymic tumors, enabling the diagnosis of these tumors and a better evaluation of their extension. It does not accumulate in thymic hyperplasia, thus allowing the differential diagnosis between these 2 pathological conditions. In patients affected by myasthenia gravis, OctreoScan scintigraphy can play an important role in characterizing thymic masses.

[18F]-FDG-PET/CT Correlates With the Response of Radiorefractory Thyroid Cancer to Lenvatinib and Patient Survival.

CONTEXT: 18F-fluoro-2-deoxy-D-glucose positron emission tomography-computed tomography ([18F]-FDG-PET/CT)-positive metastatic lesions in radioiodine-refractory differentiated thyroid cancer (RAI-R DTC) have a poor prognosis and lenvatinib represents the best therapy. OBJECTIVE: We investigated the role of [18F]-FDG-PET/CT in the evaluation of metabolic response and prediction of the outcome of RAI-R DTC patients treated with lenvatinib. METHODS: Patients (n = 33) with progressive metastatic RAI-R DTC who were treated with lenvatinib were investigated at baseline and during follow-up with biochemical (thyroglobulin and thyroglobulin antibodies), morphological (whole-body CT scan) and metabolic ([18F]-FDG-PET/CT) evaluation. RESULTS: Nineteen (57.6%) patients showed the greatest metabolic response at the first [18F]-FDG-PET/CT scan, performed after 4 weeks of lenvatinib, while 5/33 (15.1%) patients had this response later. Moreover, 66.7% of patients had both a metabolic response at the first [18F]-FDG-PET/CT scan and a morphological response at the first CT scan. We observed a correlation between the metabolic response at [18F]-FDG-PET/CT scan performed after 4 weeks of treatment and the biochemical response at the same time in 60.6% of patients. The median overall survival (OS) was significantly longer in patients with either a metabolic response at last [18F]-FDG-PET/CT (40.00 vs 8.98 months) or a morphological response at last CT scan (37.22 vs 9.53 months) than in those without response. Moreover, the OS was longer in patients with a metabolic response at [18F]-FDG-PET/CT performed after 4 weeks of treatment (36.53 vs 11.28 months). CONCLUSIONS: Our data show that [18F]-FDG-PET/CT can early predict the response to lenvatinib and correlates with the OS of RAI-R DTC patients treated with this drug.

Management of Liver Tumors during the COVID-19 Pandemic: The Added Value of Selective Internal Radiation Therapy (SIRT).

BACKGROUND: In the context of the coronavirus disease 2019 (COVID-19) pandemic, liver-directed therapies (LDTs) may offer minimally invasive integrative tools for tumor control. Among them, selective internal radiation therapy (SIRT) represents a safe, flexible and effective treatment. Purpose of this study is to present our experience with SIRT during the first wave of COVID-19 pandemic and provide an overview of the indications and challenges of SIRT in this scenario. METHODS: We retrospectively analyzed the number of patients evaluated by Multidisciplinary Liver Tumor Board (MLTB) and who were undergoing LDTs between March and July 2020 and compared it with 2019. For patients treated with SIRT, clinical data, treatment details and the best radiological response were collected. RESULTS: Compared to 2019, we observed a 27.5% reduction in the number of patients referred to MLTB and a 28.3% decrease in percutaneous ablations; transarterial chemoembolizations were stable, while SIRT increased by 64%. The majority of SIRT patients (75%) had primary tumors, mostly HCC. The best objective response and disease control rates were 56.7% and 72.2%, respectively. CONCLUSION: The first wave of the COVID-19 pandemic was characterized by an increased demand for SIRT, which represents a safe, flexible and effective treatment, whose manageability will further improve by simplifying the treatment workflow, developing user-friendly and reliable tools for personalized dosimetry and improving interdisciplinary communication.

Assessment of radiation sensitivity of unresectable intrahepatic cholangiocarcinoma in a series of patients submitted to radioembolization with yttrium-90 resin microspheres.

Radioembolization is a valuable therapeutic option in patients with unresectable intrahepatic cholangiocarcinoma. The essential implementation of the absorbed dose calculation methods should take into account also the specific tumor radiosensitivity, expressed by the α parameter. Purpose of this study was to retrospectively calculate it in a series of patients with unresectable intrahepatic cholangiocarcinoma submitted to radioembolization. Twenty-one therapeutic procedures in 15 patients were analysed. Tumor absorbed doses were calculated processing the post-therapeutic 90Y-PET/CT images and the pre-treatment contrast-enhanced CT scans. Tumor absorbed dose and pre- and post-treatment tumor volumes were used to calculate α and α3D parameters (dividing targeted liver in n voxels of the same volume with specific voxel absorbed dose). A tumor volume reduction was observed after treatment. The median of tumor average absorbed dose was 93 Gy (95% CI 81-119) and its correlation with the residual tumor mass was statistically significant. The median of α and α3D parameters was 0.005 Gy-1 (95% CI 0.004-0.008) and 0.007 Gy-1 (95% CI 0.005-0.015), respectively. Multivariate analysis showed tumor volume and tumor absorbed dose as significant predictors of the time to tumor progression. The knowledge of radiobiological parameters gives the possibility to decide the administered activity in order to improve the outcome of the treatment.

Recombinant human TSH and ablation of post-surgical thyroid remnants in differentiated thyroid cancer: the effect of pre-treatment with furosemide and furosemide plus lithium.

BACKGROUND AND AIM: Recombinant human TSH (rhTSH) can be used for post-surgical radioiodine (I-131) thyroid remnants ablation in differentiated thyroid cancer (DTC) patients after surgery. Debate exists in literature about the optimal amount of I-131 that should be given for obtaining an effective ablation and about the role of iodine pool during treatment. Therefore, the aim of the present study was to assess whether I-131 ablation during rhTSH stimulus can be improved by reducing the circulating iodine pool and by increasing thyroid cell uptake and retention of I-131 obtained by administering furosemide and lithium. METHODS: A total of 201 consecutive DTC patients were entered in the study: they were treated by total thyroidectomy and I-131 therapy during rhTSH stimulus to ablate thyroid remnants. Patients were divided into two groups according to the TNM stage: group 1 included patients in stage I-II who were treated with a low 30-mCi I-131 dose, while group 2 included patients in stage III-IV who were treated by a high 100-mCi I-131 dose. Moreover, both groups were further subdivided into three subgroups. Subgroup (a) included 45 patients from group 1 and 22 from group 2: they were treated with I-131 under rhTSH stimulus, following a short 4-day withdrawal of L-thyroxine (LT4). Subgroup (b) included 45 patients from group 1 and 22 from group 2: they were treated with I-131 under rhTSH stimulus, following a short 4-day withdrawal of L-T4, and after furosemide administration (25 mg/day orally) during the 3 days before I-131. Subgroup (c) included 45 patients from group 1 and 22 from group 2: they were treated with I-131 under rhTSH stimulus, following a short 4-day L-T4 withdrawal, and after administration of furosemide (25 mg/day orally) during the 3 days prior I-131 and lithium (450 mg/day orally) during the 3 days following I-131. Another group (group 3) of 20 patients characterized by a very low-risk cancer (unifocal tumor <1.0 cm in diameter, without extra-capsular extension, N0) was treated with a 30-mCi I-131 dose under rhTSH stimulus without performing the short 4-day L-4 withdrawal: this group was taken as the control. Follow-up was performed by neck ultrasonography (US), and Tg measurement and I-131 WBS under rhTSH stimulus. RESULTS: Among the patients from group 1, those pre-treated with furosemide or with furosemide plus lithium showed a better outcome of ablation both in terms of undetectable Tg values (97.7% and 95.5 % vs. 79.5%, p < 0.05) and of WBS negativity (97.7% vs. 81.8%, p < 0.05) during the rhTSH stimulus. No similar findings were observed in group 2 patients. Moreover, in patients from group 3 (I-131 30 mCi, without L-T4 withdrawal), the outcome of ablation was significantly lower in comparison to patients from group 1 (I-131 30 mCi, with L-T4 withdrawal) in terms of undetectable Tg during the rhTSH stimulus (55.0%, p < 0.001). CONCLUSION: rhTSH is highly effective for post-surgical thyroid remnant ablation in low-risk cancer patients using the low 30-mCi dose protocol combined with the short 4-day withdrawal of L-T4. Moreover, in these patients the pre-treatment with furosemide seems to play an important role to further improve the outcome of ablation by reducing the iodine pool.

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.

Yttrium-90 Radioembolization in Unresectable Intrahepatic Cholangiocarcinoma: Results of a Multicenter Retrospective Study.

BACKGROUND: Y90 transarterial radioembolization (Y90-RE) may improve clinical outcomes of unresectable intrahepatic cholangiocarcinoma (ICC); however, the optimal timing for Y90-RE is still debated. The purpose of this multicenter study was to retrospectively evaluate clinical outcomes of RE in patients with unresectable ICC, comparing three different settings: chemotherapy naïve patients (group A), patients with disease control after first-line chemotherapy (group B) and patients with progression after first-line chemotherapy (group C). MATERIALS AND METHODS: The study included 81 consecutive patients (49 male, mean age 62.4 ± 11.8 years): 35 (43.2%) patients were in group A, 19 (23.5%) in group B, and 27 (33.3%) in group C. Preprocedural clinical variables, tumour response according to RECIST 1.1 and overall survival (OS) were analysed and compared. RESULTS: Baseline demographic and clinical features did not differ significantly among groups, with the exception of prior surgical procedures that were significantly higher in group C patients, and macrovascular invasion that was more frequent in group B. Radiological response was available in 79 patients; objective response and disease control rates were 41.8% and 83.6%, respectively, without significant differences among groups. Median OS was 14.5 months (95% CI: 11.1-16.9) and was not significantly different among treatment groups. At multivariate analysis, tumour burden > 50%, neutrophil-to-lymphocyte (N/L) ratio ≥ 3 and radiological progression as best response resulted to be significant (P < 0.05) independent factors, negatively associated with OS. CONCLUSION: Y90-RE is a valuable treatment option in unresectable ICC, irrespectively from the timing of treatment. Tumour extension, N/L ratio and radiological response affect post-treatment survival.

Thyroid uptake of 67Ga-citrate is associated with thyroid autoimmunity and hypothyroidism in patients with sarcoidosis.

PURPOSE: To evaluate the association of gallium-67 ((67)Ga)-citrate thyroid uptake with the presence of thyroid disorders in patients with sarcoidosis (S patients). METHODS: Eighty-four S patients were evaluated by a complete thyroid work-up (neck ultrasound, circulating thyroid hormones and anti-thyroid antibodies, fine-needle aspiration). RESULTS: In S patients with (67)Ga thyroid uptake (respect those without): serum thyroid-stimulating hormone, the titre of anti-thyroid peroxidase (AbTPO) and/or anti-thyroglobulin antibodies (AbTg), and the prevalence of S patients with hypothyroidism or with positive AbTg or AbTPO was significantly higher; a thyroid hypoechoic pattern was more frequent. The prevalence of thyroid nodules was not significantly different between the two groups. Two cases of papillary thyroid cancer were observed in S patients without (67)Ga thyroid uptake, whilst no case in those with (67)Ga thyroid uptake. CONCLUSIONS: (67)Ga thyroid uptake is associated with the presence of aggressive autoimmune thyroiditis and hypothyroidism in S patients; thyroid function and ultrasonography should be performed in the presence of (67)Ga thyroid uptake.

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.

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.

Radionuclide evaluation of the lower gastrointestinal tract.

This review outlines the technical aspects and diagnostic performance parameters of nuclear medicine procedures used on patients with disorders of the lower gastrointestinal tract, with the exclusion of techniques using tumor-seeking radiopharmaceuticals. Chronic disorders of the lower gastrointestinal tract often reduce the quality of life because of discomfort from constipation or diarrhea. Five classes of radionuclide procedures are used to characterize these disorders: transit scintigraphy, searches for ectopic gastric mucosa in Meckel's diverticulum, scintigraphy of active inflammatory bowel disease, scintigraphic defecography, and scintigraphy to detect sites of gastrointestinal bleeding. Protocols for these procedures and their relative merit in patient management are discussed, with special emphasis on their potential for semiquantitative assessment of the pathophysiologic parameter investigated. Quantitation is particularly relevant for prognostic purposes and for monitoring the efficacy of therapy.

No evidence of chromosome damage in children and adolescents with differentiated thyroid carcinoma after receiving 131I radiometabolic therapy, as evaluated by micronucleus assay and microarray analysis.

PURPOSE: As (131)I therapy, used to achieve ablation of thyroid gland remnant, can cause chromosome damage in cultured peripheral lymphocytes especially, we investigated whether administration of radioiodine may induce early genome damage in peripheral T lymphocytes of adolescents with differentiated thyroid carcinoma (DTC). METHODS: We studied 11 patients, aged 14.8 +/- 3.1 years, who assumed (131)I (range: 1.11-4.44 GBq) to ablate thyroid remnant. A blood sample for micronucleus assay and for evaluating expression of some genes involved in the DNA repair or the apoptosis pathways was obtained from each patient 1 h before (T(0)) and 24 (T(1)) and 48 h (T(2)) post-radioiodine administration. RESULTS: Compared to T(0), we did not find any difference in the number of micronucleated cells at both T(1) and T(2) in any subject. Nine out of 11 patients had altered expression levels in a majority of the DNA repair and apoptosis genes at T(1), which decreased at T(2). CONCLUSIONS: We demonstrated for the first time that peripheral cells of DTC children and adolescents who received (131)I at a mean dosage of 3.50 +/- 0.37 GBq did not show chromosome damage within 48 h from the end of radiometabolic therapy. This may be due to a prompt activation of the cell machinery that maintains the integrity of the genome to prevent harmful double-strand breaks from progressing to chromosome mutations, either by repairing the lesions or by eliminating the most seriously damaged cells via apoptosis.

Intraoperative sentinel lymph node mapping in stage I non-small cell lung cancer: detection of micrometastases by polymerase chain reaction.

OBJECTIVE: We previously reported the results achieved in detecting sentinel lymph nodes (SLN). We applied the molecular techniques (RT-PCR) to improve the detection of micrometastasis in order to evaluate an improvement of staging in early non-small cell lung cancer (NSCLC) patients (pts). METHODS: This study was carried out on 22 consecutive NSCLC pts with stage I disease. A dose of 37MBq (1 ml (99m)Tc-nanocolloid suspension) was administered. The intralesional injection was performed under CT-guidance (7 pts), by using bronchoscopy (5 pts), VATS (2 pts) and at time of the thoracotomy (8 pts). RT-PCR analysis for cytokeratin 7 and 19 (CK7-CK19) was used to identify tumour-derived material in lymph nodes (LN). Each SLN was bisected: half was used for conventional examination (H&E staining/by immunohistochemistry (IHC), half was snap-frozen to -80 degrees C for RNA-detection of CK7 and CK19. RESULTS: SLN was detected in 16 out of 19 pts. In three pts SLN was not identified (due to an incorrect technique). Conventional pathologic examination showed stage I disease in 13 pts, T3N0 disease in 1 pt, N2 in 5 pts. The IHC analysis identified micrometastasis in seven pts (two evaluated N0 according to H&E staining). RT-PCR analysis, performed in 10/16 pts, identified micrometastasis in 6 pts (3 pts evaluated N0 disease by H&E ; 1 of these evaluated N0 even by IHC). All N2 patients relapsed. One patient (N0 pts after H&E and IHC analysis) with positive CK7 and CK19 expression by RT-PCR analysis relapsed (systemic relapse) 3 months after surgery. CONCLUSIONS: SLN technique could provide a subgroup of patients in which the use of RT-PCR could be applied on a well-focused target. This approach may be useful for stratifying histologically N0 patients into higher risk and lower risk groups.

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.