A modified sentinel node and occult lesion localization (SNOLL) technique in non-palpable breast cancer. A pilot study

Background: The spread of mammographic screening programs has allowed an increasing amount of early breast cancer diagnosis. A modern approach to non-palpable breast lesions requires an accurate intraoperative localization, in order to achieve a complete surgical resection. In addiction, the assessment of lymph node status is mandatory as it represents a major prognostic factor in these patients. The aim of this study is to evaluate the reliability of a modified technical approach using a single nanocolloidal radiotracer to localize both sentinel node and breast occult lesion. Methods: Twenty-five patients with a single non-palpable breast lesions and clinically negative axilla were enrolled. In the same day of surgery, patients underwent intratumoral and peritumoral administration of 99mTc-labeled nanocolloid tracer under sonographic guidance. A lymphoscintigraphy was performed to localize the sentinel lymph node and its cutaneous projection was marked on the skin in order to guide the surgeon to an optimal incision. During surgery an hand-held gamma-detection probe was used to select the best surgical access route and to guide localization of both occult breast lesion and sentinel lymph node. After specimen excision, the surgical field was checked with the gamma-probe to verify the absence of residual sources of significant radioactivity, thereby ensuring a radical treatment in a single surgical session and minimizing normal tissue excision. Results: Both targeted breast lesion and sentinel lymph node were localized and removed at the first attempt in every patients and histopathological diagnosis of malignancy was confirmed in 25/26 samples. Non-palpable lesions were included within the surgical margins in all patients and in all samples surgical margins were free from neoplastic infiltration thus avoiding any further reintervention. Only two patients showed metastatic involvement of sentinel lymph node. Conclusions: The modified sentinel node and occult lesion localization (SNOLL) technique performed with a single injection of nanocolloidal radiotracer has shown an excellent intraoperative identification rate of both non-palpable lesion and sentinel lymph node. This procedure offers, as opposed to standard techniques, an accurate, simple and reliable approach to the management of non-palpable breast cancer

Unilateral condylar hyperplasia recurrence after orthognathic surgery: a case report

Introduction: Unilateral Condylar Hyperplasia (UCH) is an uncommon condition resulting in facial asymmetry and malocclusion. At the time of diagnosis, an accurate evaluation of condylar activity through bone SPECT is necessary to determine the most appropriate surgical treatment. The Authors present a case of a UCH recurrence after orthognathic surgery in order to discuss about the clinical role of condylar SPECT in UCH therapeutic management. Case report: A 60-years old female patient was referred to the Department of Maxillo-Facial Surgery of Sapienza University of Rome for a relapse of mandibular laterodeviation. At the age of 24, she underwent orthognathic surgery after a diagnosis of UCH without condylar SPECT evaluation. As part of our clinical routine, condylar SPECT was performed and a significant difference in radiotracer uptake (20%) was found between the left condylar region and the contralateral one. She underwent high condilectomy and Bilateral Mandibular Sagittal Osteotomy. She had no evidence of recurrence till today. Discussion: Optimal surgical management of UCH is still controversial. In the diagnostic phase of UCH, a functional evaluation of condylar growth status by bone SPECT is an essential step to avoid long-term recurrence of mandibular asymmetry. On the basis of condylar metabolic activity, UCH can be classified in an active phase or a stationary phase. Clinical and functional evaluation of patients with mandibular asymmetry should be standardized in order to plan the most appropriate surgical and orthodontic treatment

Safety and Efficacy of Combined Peptide Receptor Radionuclide Therapy and Liver Selective Internal Radiation Therapy in a Patient With Metastatic Neuroendocrine Tumor

Nuclear medicine treatments of well-differentiated neuroendocrine tumors (NETs) are gaining increasing acceptance among clinicians. Peptide receptor radionuclide therapy (PRRT) is an effective systemic treatment, providing a significant survival benefit and improving patients' quality of life. Locoregional selective internal radiation therapy (SIRT) is a safe and effective treatment for unresectable NET liver metastases, providing good local tumor control and symptomatic relief. Few reports in literature examine the sequential use of PRRT and SIRT in metastatic NET. We report the case of a metastatic NET patient treated with sequential PRRT-SIRT achieving a long disease control interval without cumulative toxicity issues

Ra-223 dichloride management in a Nuclear Medicine Unit: experience of a referral institution

Ra-223 dichloride is a first-in-class alpha-emitting radiopharmaceutical recently introduced into clinical practice for treatment of men with Castration-Resistant Prostate Cancer (CRPC) and symptomatic bone metastases. Due to the proven benefit on Overall Survival and the favorable toxicity profile, Ra-223 therapy is gaining widespread use in both US and Europe. In this article, we describe the routinary management of patients undergoing Ra-223 treatment in our Institution. Currently, Ra-223 therapy is indicated for 6 intravenous injections (55 kBq per kg of body weight) administered every 28 days. In comparison to other radiopharmaceuticals, Ra-223 handling and administration do not need any additional training for authorized users. Due to the minimal external dose rate emission, Ra-223 dichloride can be delivered in an outpatient setting. Moreover, no particular precautions other than standard hygiene measures must be taken by patients’ family members or caregivers. Ra-223 therapy is associated to a favorable hematologic toxicity profile, while non-hematologic adverse events are generally mild and easy to manage. Given the favorable toxicity profile of this treatment, clinical trials are currently ongoing to evaluate efficacy and safety of Ra-223 treatment in combination or sequence with recently approved drugs such as abiraterone acetate, enzalutamide and sipuleucel-T. In addition, the recent interest in Ra-223 bone lesion dosimetry could open the way to a dosimetric-based therapeutic approach with Ra-223. In this new scenario, results of these promising clinical trials may help clarifying the optimal sequencing of new therapeutic possibilities for metastatic CRPC and the appropriate eligibility criteria for Ra-223 treatment in oncologic patients

HMGB1 expression in leukocytes as a biomarker of cellular damage induced by [99mTc]Tc-HMPAO-labelling procedure: a quality control study

Purpose. Autologous White Blood Cells (WBC) scintigraphy is based on a multi-step sequence of cell separation and radiolabelling. Besides in vivo imaging quality control, no molecular tool is available to evaluate WBC damage secondary to cell manipulation. High Mobility Group Box 1 (HMGB1) is a protein of the alarmins family, secreted by innate immune cells and released from the nucleus of damaged cells following different types of injury. Aim of this study was to evaluate HMGB1 levels in WBC cytosolic extracts (CE) before and after [99mTc]Tc-HMPAO labelling procedure, as a biomarker of induced WBC damage. Procedures. Patients with suspect of prosthetic joint infection were prospectively enrolled. HMGB1 levels were evaluated by immunoblotting analysis in plasma (t0), and in WBC-CE before (t1) and after (t2) [99mTc]Tc-HMPAO labelling. Blood samples from healthy subjects were evaluated under the same procedure. Results. Twenty consecutive patients referred for WBC scintigraphy and ten controls were enrolled. HMGB1 levels were significantly upregulated both in plasma (t0) and in circulating WBC-CE (t1) from patients compared to controls (p<0.0001). Otherwise, WBC-CE from [[99mTc]Tc-HMPAO-labelled leukocyte concentrate (t2) did not show significant changes in HMGB1 levels compared to the cold leukocyte sample (t1). Conclusions. The evaluation of HMGB1 levels in WBC-CE from each subject after radiolabelling with [99mTc]Tc-HMPAO did not show significant changes compared to the cold cellular sample. These results further prove the reliability of [99mTc]Tc-HMPAO leukocyte radiolabelling procedure in terms of cell viability and suggest that the monitoring of this alarmin may represent a specific tool to evaluate a secondary damage of WBC induced by radiolabelling procedure. In addition, significant upregulation of HMGB1 levels was found in WBC-CE and in plasma from patients with suspect of PJI - compared to healthy donors - reasonably related to their underlying inflammatory/infective condition

Prostate-specific antigen flare phenomenon during 223Ra-Dichloride treatment for bone metastatic castration-resistant prostate cancer: a case report

223Ra-dichloride is an alpha-emitting radionuclide recently approved for for treatment of CRPC patients with symptomatic bone metastases. In this specific therapeutic setting, PSA is not an objective biomarker in assessing 223Ra efficacy. We present as case of a 79-years old patient affected by CRPC and symptomatic bone metastases enrolled in the 223Ra-dichloride Early Access Program who presented a relevant rise in PSA levels after the fifth 223Ra administration. No radiological signs of disease progression were found, so this event was recognized as a PSA flare phenomenon and last 223Ra infusion was administered. In clinical practice, PSA flare in the course of 223Ra treatment can be misinterpreted as a therapeutic failure with early withdrawal from a potentially effective therapy. During 223Ra treatment, PSA flare can be explained as a direct consequence of 223Ra cytotoxic effect on cancer cells. Further analysis should be conducted on large cohort in order to evaluate the clinical significance of PSA flare phenomenon during 223Ra treatm

Why SLNB procedure is not currently used in early stage oral squamous cell carcinoma?

Since its introduction in 1970s, Sentinel Lymph Node Biopsy (SLNB) has become a standard of care to stage nodal status in melanoma, breast cancer and some gynecological cancers. In 2014 this procedure was incorporated into National Comprehensive Cancer Network (NCCN) guidelines for stage I-II oral squamous cell carcinoma (OSCC) as a reliable alternative to Elective Neck Dissection (END) [1,2]. Recent studies reported that SLNB is still rarely used in patients with OSCC, notwithstanding the fact that SLNB has been shown to be com- parable to END in terms of Overall Survival [1,3–5]. Compared to END, SLNB can provide a significant reduction in post- operative morbidity particularly in OSCC involving subsites such as the floor of the mouth or the ventral surface of tongue, in which en-bloc resection of primary tumor and cervical lymph nodes requires im- mediate reconstruction using flap

Radiopharmaceuticals labelled with copper radionuclides: clinical results in human beings

Positron emission tomography (PET) is an instrumental diagnostic modality developed around the positron-emitting radioisotopes of biologically important elements such as carbon, oxygen and nitrogen (11C, 15O, 13N). Among longer-lived PET radionuclides, 18F is by far the most commonly used radiotracer, extensively used for tumour imaging with FDG ([18F]-fluorodeoxyglucose) and also frequently investigated in the development of novel radiopharmaceuticals. Many other positron- emitting radionuclides with higher atomic numbers and longer half-lives have been investigated for both imaging and therapeutic purposes, including the halogens (124I, 120I, 76Br) and a number of metal radionuclides. The radio-copper has attracted considerable attention, because they include isotopes which, due to their emission properties, offer themselves as agents of both diagnostic imaging (60Cu, 61Cu, 62Cu, 64Cu) and in vivo targeted radiation therapy (64Cu and 67Cu)

In vivo microbial targeting of 99mTc-Labeled Human β-Defensin-3 in a rat model of infection

Differentiation of infection from aseptic inflammation represents a major clinical issue. None of the commercially available compounds (labeled granulocytes, antigranulocyte antibodies, Ga-citrate, labeled immunoglobulin G, F-FDG) is capable of this differentiation, producing a nonnegligible false-positive rate. Recently, our group reported on a reliable labeling procedure of the antimicrobial peptide human β-defensin 3 (HBD-3) with Tc. The aim of this study was to evaluate in vivo Tc-HBD-3 uptake in a rat model of infection

Radio-localization of non-palpable breast lesions under ultrasonographic guidance: current status and future perspectives

Background: Due to the spread of mammographic screening programs, a constant increase of clinically-occult breast cancer diagnosis has been registered. A correct approach to nonpalpable breast lesions requires an accurate intra-operative localization in order to achieve a complete surgical resection. The aim of this paper is to describe the state of the art of the US-guided procedures such as Radio-guided Occult Lesion Localization (ROLL) and Radio-guided Seed Localization (RSL) in comparison to the most widely adopted Wire-Guided Localization (WGL). Methods: Links to full text papers and abstracts published in the last 25 years regarding localization of non-palpable breast lesions were researched using PubMed service of US National Library of Medicine. Using the term “non-palpable breast lesions localization”, different localization techniques were considered and analyzed. Human studies, published in English, French, German, Italian, and Spanish in journals with an impact factor index, were taken into account, independently of the type of article (clinical trial, review, editorial, etc.) or radiopharmaceutical used. Since the aim was to assess the clinical value of the procedures, a higher relevance was assigned to studies with significantly high number of patients and to those comparing at least two localization techniques. The reliability of each technique was evaluated taking into account several parameters such as correlation index between two localization procedures, risk of complications, lesion margin involvement and rate re-operation. Conclusions: Since their introduction in clinical practice, several randomized clinical trials and meta-analyses showed the accuracy and reliability of radio-guided procedures performed under ultrasonographic guidance