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Purpose: Sentinel lymph node biopsy is an essential staging tool in patients with clinically localized oral cavity squamous cell carcinoma. The harvesting of a sentinel lymph node entails a sequence of procedures with participation of specialists in nuclear medicine, radiology, surgery, and pathology. The aim of this document is to provide guidelines for nuclear medicine physicians performing lymphoscintigraphy for sentinel lymph node detection in patients with early N0 oral cavity squamous cell carcinoma., Methods: These practice guidelines were written and have been approved by the European Association of Nuclear Medicine (EANM) and the International Atomic Energy Agency (IAEA) to promote high-quality lymphoscintigraphy. The final result has been discussed by distinguished experts from the EANM Oncology Committee, and national nuclear medicine societies. The document has been endorsed by the Society of Nuclear Medicine and Molecular Imaging (SNMMI). These guidelines, together with another two focused on Surgery and Pathology (and published in specialised journals), are part of the synergistic efforts developed in preparation for the "2018 Sentinel Node Biopsy in Head and Neck Consensus Conference"., Conclusion: The present practice guidelines will help nuclear medicine practitioners play their essential role in providing high-quality lymphatic mapping for the care of early N0 oral cavity squamous cell carcinoma patients.

In this short review, the technical and clinical improvements of the sentinel lymph node biopsy in head and neck cancer are presented.

Purpose: Optimum management of the N0 neck is unresolved in oral cancer. Sentinel node biopsy (SNB) can reliably detect microscopic lymph node metastasis. The object of this study was to establish whether the technique was both reliable in staging the N0 neck and a safe oncological procedure in patients with early-stage oral squamous cell carcinoma., Methods: An European Organisation for Research and Treatment of Cancer-approved prospective, observational study commenced in 2005. Fourteen European centres recruited 415 patients with radiologically staged T1-T2N0 squamous cell carcinoma. SNB was undertaken with an average of 3.2 nodes removed per patient. Patients were excluded if the sentinel node (SN) could not be identified. A positive SN led to a neck dissection within 3 weeks. Analysis was performed at 3-year follow-up., Results: An SN was found in 99.5% of cases. Positive SNs were found in 23% (94 in 415). A false-negative result occurred in 14% (15 in 109) of patients, of whom eight were subsequently rescued by salvage therapy. Recurrence after a positive SNB and subsequent neck dissection occurred in 22 patients, of which 16 (73%) were in the neck and just six patients were rescued. Only minor complications (3%) were reported following SNB. Disease-specific survival was 94%. The sensitivity of SNB was 86% and the negative predictive value 95%., Conclusion: These data show that SNB is a reliable and safe oncological technique for staging the clinically N0 neck in patients with T1 and T2 oral cancer. EORTC Protocol 24021: Sentinel Node Biopsy in the Management of Oral and Oropharyngeal Squamous Cell Carcinoma., (Copyright © 2015. Published by Elsevier Ltd.)

Aim: To evaluate the role of dynamic lymphoscintigraphy with a same-day protocol for sentinel node biopsy in oral cavity cancer., Methods: Twenty-two consecutive patients affected by cT1-2N0 squamous cell carcinoma of the oral cavity were enrolled between September 2001 and November 2005. After a local anaesthetic (10% lidocaine spray), a dose of 30-50 MBq of Tc human serum albumin nanocolloid, in ml saline, was injected superficially (1-2 mm subendothelial injection) into four points around the lesion. Dynamic lymphoscintigraphy was acquired immediately (256x256 matrix, 5 min pre-set time, LEGP collimator) in lateral and anterior projections. The imaging was prolonged until the lymph nodes of at least two neck levels were visualized (time required min). About 3 h later (same-day protocol) the patients had a radioguided sentinel node biopsy. Elective neck dissection was performed in the first 13 patients; whereas the last nine patients had elective neck dissection only if the sentinel node was positive. Sentinel nodes were dissected into 1 mm thick block sections and studied by haematoxylin & eosin staining and immunohistochemistry (anticytokeratin antibody)., Results: The sentinel nodes were found on the 1st neck level in 13 cases, on the 2nd neck level in eight cases, and on the 3rd neck level in one case (100% sensitivity). The average number of sentinel nodes was 2.2 for each patient. The sentinel node was positive in eight patients (36%); with six of them having the sentinel node as the exclusive site of metastasis. No skip metastases were found in the 14 patients with negative sentinel node (100% specificity)., Conclusion: Our preliminary data indicate that superficial injections of radiocolloid and dynamic lymphoscintigraphy provide a high success rate in sentinel node identification in oral cavity cancers. Dynamic lymphoscintigraphy helps in distinguishing sentinel node from second-tier lymph nodes. The same-day protocol is advisable in order to correctly identify the first sentinel node, avoiding multiple and unnecessary node biopsies, without reducing sensitivity.

Aims: Cutaneous squamous cell carcinoma (SCC) is the second most common skin cancer. The metastatic potential is generally low. However, there are subgroups of patients at higher risk, for whom sentinel lymph node biopsy (SLNB) might be useful. SLNB might allow the timely inclusion of high risk patients in more aggressive treatment protocols, sparing at the same time node-negative patients the morbidity of potentially unnecessary therapy. Our aim was to introduce the concept of SLNB for patients with high risk cutaneous SCC., Patients and Methods: We examined a consecutive series of high risk cutaneous SCC patients undergoing SLNB at our large dermatological hospital, and performed a literature review and pooled analysis of all published cases of SLNB for cutaneous SCC., Results: Among the 22 clinically node-negative patients undergoing SLNB at our hospital, one patient (4.5%) showed a histologically positive sentinel node and developed recurrences during follow-up. Sentinel node-negative patients showed no metastases at a median follow-up of 17 months (range: 6-64). The incidence of positive sentinel nodes in previous reports ranged between 12.5% and 44.4%. Pooling together patients from the present and previous studies (total 83 patients), we calculated an Odds Ratio of 2.76 (95% CI 1.2-6.5; p=0.02) of finding positive sentinel nodes for an increase in tumor size from <2 cm to 2.1-3 cm to >3 cm., Conclusions: Our case series and the pooled analysis support the concept that SLNB can be performed for high risk cutaneous SCC. Prospective multicenter studies are needed to examine the role, utility and cost-effectiveness of SLNB for this population.

The routine use of a sentinel node biopsy (SNB) protocol in oral cavity squamous cell carcinomas (SCC) has been challenged on the basis of the elevated number of sentinel nodes (SNs) detected (>2.5) and on the multiply neck level involvement reported in several studies. These data limit the practical application of the protocol, because in such cases, it seems easier and safer to perform a selective neck dissection. The aim of our study is to perform radioguided surgery 1-3 h after lymphoscintigraphy (same day protocol) to detect the lymph nodes closest to the tumour site. In our study, 12 patients affected by cT1-2 N0 SCC of the oral cavity were submitted to a same day protocol of a lymphoscintigraphic examination (1-3 h before surgery) and a radioguided SNB. We used a hand-held gamma probe and performed an elective neck dissection on all patients. The SNs were found in all cases with 83% localised in the ipsilateral neck in only levels I-II. The mean number of SN detected was 2.1, with a mean pathological size of 13.8 mm measured on pathological specimen. Metastases were found in 5/12 cases (41.6%), on levels I, II and III and all were identified by step serial sectioning and routine H&E staining. This study confirms the accuracy of SNB in predicting the presence of occult metastases. This protocol is designed to detect SNs, which are almost always on neck level I and II, thereby limiting the number of nodes examined and the extension of the surgical approach.

Background: The purpose of this paper is to present personal experience with sentinel node biopsy for the treatment of malignant melanoma. Technical details influencing the efficacy of the procedure are presented and the clinical, therapeutic and prognostic advantages of this technique discussed., Methods: A total of 390 consecutive patients with primary skin melanoma (T2-3,N0,M0) underwent sentinel node biopsy between March 1996 and May 2001. All patients underwent previous excisional biopsy of the primary lesion and clinical and radiographic examination to exclude lymphatic or systemic macroscopic spreading of the disease. Preoperative lymphoscintigraphy (99mTc nanocoll) was routinely performed in the last 315 patients. Intraoperative detection of the sentinel nodes was performed by perilesional, intradermical, injection of blue dye associated with a g probe (Neoprobe(R) 2000) in the last 315 patients. Sentinel nodes, serially sectioned, were all Haematoxylin-Eosin and immunohistochemically stained. All patients positive for micro-metastasis underwent radical lymphadenectomy. Comparative analysis between the incidence of metastasis in sentinel and non-sentinel nodes, according to the clinical stage of the disease, was done., Results: The overall detection rate of sentinel nodes was 97.4%. Relevant differences were found according to the site of dissection and the use of a g probe. The g-probe makes the procedure more effective, less invasive and less expensive. Timing and accuracy of the preoperative lymphoscintigraphy is a basic step of the procedure. The overall incidence of positive sentinel nodes was 14.7% with differences correlated with thickness of primary lesion (0.75-1.5 mm: 5,8%; 1.5-3 mm:18%; 3-4 mm: 24.6%). Metastasis in other non-sentinel nodes was found only with primary tumour thickness exceeding 2 mm., Conclusions: Sentinel node biopsy is a procedure requiring a multidisciplinary approach (surgery, nuclear medicine and pathology). A specific learning phase (>30 patients) is recommended to obtain reliable results.

Aim: The aim of our study was to evaluate the role of scintigraphy in lymphatic mapping and in the identification of the sentinel lymph node (SLN) in patients with head and neck cancer., Methods: Between September 1999 and February 2001 we enrolled 22 consecutive patients with cancer in the head and neck region: five squamous cell carcinomas, one Merkel cell tumor of the cheek, and 16 malignant melanomas. Lymphoscintigraphy was performed three hours before surgery after injection of 30-50 MBq of 99mTc -Nanocoll in 0.3 mL; the dose was fractionated by injecting the radiotracer at two points around the lesion. Static acquisition (anterior and/or lateral views, 512 x 512 matrix, 5 mins pre-set time) was started immediately after the injections so as to visualize the pathways of lymphatic drainage. The skin projection of the SLN was marked with ink. Intraoperative SLN detection was performed with perilesional injection of patent blue., Results: SLNs were found with lymphoscintigraphy in all patients. Thirty-three SLNs were identified: one occipital node, three nodes at the base of the tongue, 10 superficial lateral nodes (external jugular), five submandibular nodes, five submental nodes, three mastoid nodes and six supraclavicular nodes. Biopsy was performed in 21/22 patients. In 20/22 patients the first lymph nodes were visualized in the proximal cranial regions (retroauricular, jugular and submandibular) at five minutes post injection. The SLN positivity rate was 13.6% (three patients). All patients with tumor-positive SLNs were submitted to radical dissection. Poor concordance in the detection of sentinel nodes was observed with patent blue., Conclusions: The flow of nanocolloid in the lymph vessels of the head is rapid. In our experience immediate scintigraphic imaging was essential to visualize the pathways of lymphatic drainage and the first SLN. Radioguided SLN biopsy is therefore recommended within three hours. Injection of patent blue is inadvisable because of the poor concordance with lymphoscintigraphy and the risk of permanent tattooing of the face.

Purpose: To optimize the lymphoscintigraphic procedure in the staging of malignant cutaneous melanoma., Material and Methods: Fifty-five patients (21 men and 34 women) were enrolled. Breslow thickness of the lesions ranged 0.75-1 mm (Clark III-IV) to 1-4 mm. Lymphoscintigraphy was performed with a large-view gamma camera equipped with a low-energy general purpose collimator, two weeks after melanoma excision. A single perilesional dose of 30-50 MBq nanocoll-Tc99m (volume 0.2-0.3 mL) was injected 18 hours before surgery (6 hours in head localizations). After injection a gentle local massage was applied. A planar static scintigraphy (matrix 512 x 512, pre-set time 5 min) in anterior and/or oblique view(s) was obtained 5-10 min after radiotracer injection. The skin projection of the first node was stained with an external radioactive marker. Fifteen minutes before surgery a blue-vital dye was injected around the lesion. A radioguided biopsy of the sentinel node was performed., Results: The site of the sentinel node was typical in 80% of patients. Two or three nodes were identified in 20% of patients. An unexpected node site was detected in 9% of patients. The total rate of micrometastasis to the sentinel node was 14.7% but significant differences were observed relative to the melanoma thickness., Conclusions: Preoperative scintigraphy increases the accuracy of sentinel node identification in unusual lymphatic drainage pathways, in unexpected sites and in fast lymphatic drainage. Radioguided biopsy reduces surgical time, requires only local anesthesia and permits shorter hospitalization.

Aims and Background: Sentinel node (SN) biopsy has been introduced to solve the controversy concerning the effectiveness of prophylactic lymphadenectomy in intermediate thickness melanoma. The aim of this study was to evaluate the rate of metastases, the technical details of the procedure, and the main reasons of failure., Methods: 235 patients affected by intermediate thickness melanoma (tumor thickness >0.75 mm and <4 mm) without clinical signs of systemic spread (N0M0) were submitted to sentinel node biopsy between 1996 and 2000. Preoperative lymphoscintigraphy was routinely performed in the last 184 patients. Intraoperative mapping with gamma probe was combined with the use of vital dye for identification of sentinel nodes in the last 113 patients., Results: The SN detection rate was 95.6%, with significant differences depending on the site of dissection and the use of a gamma probe. The overall rate of micrometastases was 14.7%, but relevant differences were recorded between different subgroups of patients (T2, 5.1%; T3a, 19.6%; T3b, 29%)., Conclusions: Sentinel node biopsy requires a multidisciplinary approach (surgery, pathology and nuclear medicine) for reliable results. The association of vital dye and intraoperative gamma probe for sentinel node harvesting has made the procedure more effective, less time-consuming and less invasive. Failures may be due not only to surgical mistakes, but also to improper nuclear medicine procedures or inaccurate histological evaluation of SNs. Methods for histological examination of the SN are still debated and not standardized but promising results have recently been obtained with molecular oncology techniques (RT-PCR).