The potential of the Crystal Cam handheld gamma-camera for preoperative and intraoperative sentinel lymph node localization in early-stage oral cancer.

PURPOSE: Evaluating the Crystal Cam handheld gamma-camera for preoperative and intraoperative sentinel lymph node (SLN) localization in early-stage oral cancer. METHODS: The handheld gamma-camera was used complementary to conventional gamma-probe guidance for intraoperative SLN localization in 53 early-stage oral cancer patients undergoing SLN biopsy. In 36 of these patients, a blinded comparison was made between preoperative handheld gamma-camera and lymphoscintigraphy outcomes. Of those, the reliability for marking the SLN's location using both handheld gamma-camera and a 57Co-penpoint marker was evaluated in 15 patients. RESULTS: In the entire cohort, the handheld gamma-camera preoperatively detected 116/122 (95%) of SLNs identified by lymphoscintigraphy. In those patients where the observer was blinded for lymphoscintigraphy (n = 36), 71/77 (92%) SLNs were correctly identified by handheld gamma-camera. Overlooked SLNs by handheld gamma-camera were mainly located near the injection site. The SLN's marked location by handheld gamma-camera and 57Co-penpoint marker was considered accurate in 42/43 (98%) SLNs. The intraoperative use of the handheld gamma-camera led to the extirpation of 16 additional 'hot' lymph nodes in 14 patients, 4 of which harbored metastases, and prevented 2 patients (4%) from being erroneously staged negative for nodal metastasis. In those with follow-up ≥ 24 months or false-negative outcomes < 24 months following SLNB, a sensitivity of 82% and negative predictive value of 93% was obtained. CONCLUSION: The Crystal Cam handheld gamma-camera offers reliable preoperative and intraoperative SLN localization and might reduce the risk of missing a malignant SLN during surgery. Detecting SLNs near the injection site by handheld gamma-camera remains challenging.

Within-patient comparison between [68Ga]Ga-tilmanocept PET/CT lymphoscintigraphy and [99mTc]Tc-tilmanocept lymphoscintigraphy for sentinel lymph node detection in oral cancer: a pilot study.

PURPOSE: To compare sentinel lymph node (SLN) identification using [68Ga]Ga-tilmanocept PET/CT lymphoscintigraphy to [99mTc]Tc-tilmanocept lymphoscintigraphy (including SPECT/CT) in early-stage oral cancer. Furthermore, to assess whether reliable intraoperative SLN localization can be performed with a conventional portable gamma-probe using [99mTc]Tc-tilmanocept without the interference of [68Ga]Ga-tilmanocept in these patients. METHODS: This prospective within-patient comparison pilot study evaluated SLN identification by [68Ga]Ga-tilmanocept PET/CT lymphoscintigraphy compared to conventional lymphoscintigraphy using [99mTc]Tc-tilmanocept (~ 74 MBq) in 10 early-stage oral cancer patients scheduled for SLN biopsy. After conventional [99mTc]Tc-tilmanocept lymphoscintigraphy, patients underwent peritumoral administration of [68Ga]Ga-tilmanocept (~ 10 MBq) followed by PET/CT acquisition initiated 15 min after injection. Intraoperative SLN localization was performed under conventional portable gamma-probe guidance the next day; the location of harvested SLNs was correlated to both lymphoscintigraphic images in each patient. RESULTS: A total of 24 SLNs were identified by [99mTc]Tc-tilmanocept lymphoscintigraphy, all except one were also identified by [68Ga]Ga-tilmanocept PET/CT lymphoscintigraphy. [68Ga]Ga-tilmanocept PET/CT lymphoscintigraphy identified 4 additional SLNs near the injection site, of which two harbored metastases. Lymphatic vessels transporting [68Ga]Ga-tilmanocept were identified by PET/CT lymphoscintigraphy in 80% of patients, while draining lymphatic vessels were visualized by [99mTc]Tc-tilmanocept lymphoscintigraphy in 20% of patients. Of the 33 SLNs identified by [68Ga]Ga-tilmanocept PET/CT lymphoscintigraphy, 30 (91%) were intraoperatively localized under conventional gamma-probe guidance. CONCLUSION: [68Ga]Ga-tilmanocept PET/CT lymphoscintigraphy provided more accurate identification of SLNs and improved visualization of lymphatic vessels compared to [99mTc]Tc-tilmanocept lymphoscintigraphy. When combined with peritumoral administration of [99mTc]Tc-tilmanocept, SLNs detected by [68Ga]Ga-tilmanocept PET/CT lymphoscintigraphy can be reliably localized during surgery under conventional gamma-probe guidance.

Sentinel lymph node detection in oral cancer: a within-patient comparison between [99mTc]Tc-tilmanocept and [99mTc]Tc-nanocolloid.

PURPOSE: Sentinel lymph node (SLN) biopsy has proven to reliably stage the clinically negative neck in early-stage oral squamous cell carcinoma (OSCC). [99mTc]Tc-tilmanocept may be of benefit in OSCC with complex lymphatic drainage patterns and close spatial relation to SLNs. METHODS: A prospective within-patient evaluation study was designed to compare [99mTc]Tc-tilmanocept with [99mTc]Tc-nanocolloid for SLN detection. A total of 20 patients with early-stage OSCC were included, who underwent lymphoscintigraphy with both tracers. Both lymphoscintigraphic images of each patient were evaluated for SLN detection and radiotracer distribution at 2-4 h post-injection. RESULTS: The injection site's remaining radioactivity was significantly lower for [99mTc]Tc-tilmanocept (29.9%), compared with [99mTc]Tc-nanocolloid (60.9%; p < 0.001). Radioactive uptake in SLNs was significantly lower for [99mTc]Tc-tilmanocept (1.95%) compared with [99mTc]Tc-nanocolloid (3.16%; p = 0.010). No significant difference was seen in SLN to injection site ratio in radioactivity between [99mTc]Tc-tilmanocept (0.066) and [99mTc]Tc-nanocolloid (0.054; p = 0.232). A median of 3.0 and 2.5 SLNs were identified with [99mTc]Tc-tilmanocept and [99mTc]Tc-nanocolloid, respectively (p = 0.297). Radioactive uptake in higher echelon nodes was not significantly different between [99mTc]Tc-tilmanocept (0.57%) and [99mTc]Tc-nanocolloid (0.86%) (p = 0.052). A median of 2.0 and 2.5 higher echelon nodes was identified with [99mTc]Tc-tilmanocept and [99mTc]Tc-nanocolloid, respectively (p = 0.083). CONCLUSION: [99mTc]Tc-tilmanocept had a higher injection site clearance, but at the same time a lower uptake in the SLN, resulting in an SLN to injection site ratio, which was not significantly different from [99mTc]Tc-nanocolloid. The relatively low-radioactive uptake in SLNs of [99mTc]Tc-tilmanocept may limit intraoperative detection of SLNs, but can be overcome by a higher injection dose.

Superomedial partial arytenoidectomy for voice improvement by correction of posterior glottic insufficiency.

PURPOSE: Arytenoid resection is a well-known intervention to improve glottic airway. Superomedial partial arytenoidectomy (SPA) can also be used for voice improvement by correcting posterior glottic insufficiency in patients with an obstructing anteromedially prolapsed arytenoid. Posterior glottic insufficiency can be difficult to address and traditionally involves challenging arytenoid repositioning procedures. This study aimed to compare postoperative functional voice outcomes in patients who underwent SPA to pre-operative voice status. Second, consequences of concomitant injection augmentation in patients who underwent SPA were studied. Additionally, presenting the surgical technique. METHODS: In this retrospective cohort study, pre-operative and postoperative clinical data of patients who underwent SPA between 2004 and 2018 were analyzed. Both short- and long-term voice outcomes were assessed using Voice Handicap Index (VHI) and maximum phonation time (MPT). Pre- to postoperative assessment changes (delta: δ) were applied to multivariate analyses. RESULTS: A total of 105 patients were included, of which 91 had hemilaryngeal immobility, 25 had undergone previous phonosurgical procedures and 45 received concomitant injection augmentation. Patients who underwent SPA had significant improvement of VHI and MPT. In 81% of our population, laryngeal framework surgery was avoided. Multivariate analyses showed significantly improved short-term voice outcomes in patients who received injection augmentation concomitantly to SPA. Finally, δMPT was a significant predicting factor regarding additional procedures in patients who underwent SPA. CONCLUSION: SPA is a safe and efficient procedure for voice improvement in patients with posterior glottic insufficiency due to an obstructing anteromedially prolapsed arytenoid. We recommend performing this procedure combined with injection augmentation.

CT Lymphography Using Lipiodol® for Sentinel Lymph Node Biopsy in Early-Stage Oral Cancer.

This study evaluated sentinel lymph node (SLN) identification with CT lymphography (CTL) following peritumoral administration of Lipiodol® relative to conventional 99mTc-nanocolloid lymphoscintigraphy (including SPECT/CT) in 10 early-stage oral cancer patients undergoing SLN biopsy. Patients first underwent early dynamic and static scintigraphy after peritumoral administration of 99mTc-nanocolloid. Subsequently, Lipiodol® was administered at the same injection sites, followed by fluoroscopy and CT acquisition. Finally, late scintigraphy and SPECT/CT were conducted, enabling the fusion of late CTL and SPECT imaging. The next day, designated SLNs were harvested, radiographically examined for Lipiodol® uptake and histopathologically assessed. Corresponding images of CT, 99mTc-nanocolloid lymphoscintigraphy and SPECT/late CTL fusion were evaluated. 99mTc-nanocolloid lymphoscintigraphy identified 21 SLNs, of which 7 were identified with CTL (33%). CTL identified no additional SLNs and failed to identify any SLNs in four patients (40%). Out of six histopathologically positive SLNs, two were identified by CTL (33%). Radiographic examination confirmed Lipiodol® uptake in seven harvested SLNs (24%), of which five were depicted by CTL. CTL using Lipiodol® reached a sensitivity of 50% and a negative predictive value (NPV) of 75% (median follow-up: 12.3 months). These results suggest that CTL using Lipiodol® is not a reliable technique for SLN mapping in early-stage oral cancer.

Evaluation of a streamlined sentinel lymph-node imaging protocol in early-stage oral cancer.

OBJECTIVE: Sentinel lymph-node (SLN) mapping for early-stage oral squamous cell carcinoma (OSCC) is comprehensive and consequently time-consuming and costly. This study evaluated the clinical value of several SLN imaging components and analyzed the accuracy for SLN identification using a streamlined SLN imaging protocol in early-stage OSCC. MATERIALS AND METHODS: This retrospective within-patient evaluation study compared both number and localization of identified SLNs between the conventional SLN imaging protocol and a streamlined imaging protocol (dynamic lymphoscintigraphy (LSG) for 10 min directly post-injection and SPECT-CT at ~ 2 h post-injection). LSG and SPECT-CT images of 77 early-stage OSCC patients, scheduled for SLN biopsy, were evaluated by three observers. Identified SLNs using either protocol were related to histopathological assessment of harvested SLNs, complementary neck dissection specimens and follow-up status. RESULTS: A total of 200 SLNs were identified using the streamlined protocol, and 12 additional SLNs (n = 212) were identified with the conventional protocol in 10 patients. Of those, 9/12 were identified on early static LSG and 3/12 on late static LSG. None of the additionally identified SLNs contained metastases; none of those in whom additional SLNs were identified developed regional recurrence during follow-up. Only inferior alveolar process carcinoma showed a higher rate of additionally identified SLNs with the conventional protocol (p = 0.006). CONCLUSION: Early dynamic LSG can be reduced to 10 min. Late static LSG may be omitted, except in those with a history of oncological neck treatment or with OSCC featuring slow lymphatic drainage. Early static LSG appeared to be contributory in most OSCC subsites.

Contralateral Regional Recurrence in Lateralized or Paramedian Early-Stage Oral Cancer Undergoing Sentinel Lymph Node Biopsy-Comparison to a Historic Elective Neck Dissection Cohort.

Introduction: Nowadays, two strategies are available for the management of the clinically negative neck in early-stage (cT1-2N0) oral squamous cell carcinoma (OSCC): elective neck dissection (END) and sentinel lymph node biopsy (SLNB). SLNB stages both the ipsilateral and the contralateral neck in early-stage OSCC patients, whereas the contralateral neck is generally not addressed by END in early-stage OSCC not involving the midline. This study compares both incidence and hazard of contralateral regional recurrences (CRR) in those patients who underwent END or SLNB. Materials and Methods: A retrospective multicenter cohort study, including 816 lateralized or paramedian early-stage OSCC patients, staged by either unilateral or bilateral END (n = 365) or SLNB (n = 451). Results: The overall rate of occult contralateral nodal metastasis was 3.7% (30/816); the incidence of CRR was 2.5% (20/816). Patients who underwent END developed CRR during follow-up more often than those who underwent SLNB (3.8 vs. 1.3%; p = 0.018). Moreover, END patients had a higher hazard for developing CRR than SLNB patients (HR = 2.585; p = 0.030). In addition, tumor depth of invasion was predictive for developing CRR (HR = 1.922; p = 0.009). Five-year disease-specific survival in patients with CRR was poor (42%) compared to patients in whom occult contralateral nodal metastases were detected by SLNB or bilateral END (88%), although not statistically different (p = 0.066). Conclusion: Our data suggest that SLNB allows for better control of the contralateral clinically negative neck in patients with lateralized or paramedian early-stage OSCC, compared to END as performed in a clinical setting. The prognosis of those in whom occult contralateral nodal metastases are detected at an earlier stage may be favorable compared to those who eventually develop CRR, which highlights the importance of adequate staging of the contralateral clinically negative neck.

New Developments in Imaging for Sentinel Lymph Node Biopsy in Early-Stage Oral Cavity Squamous Cell Carcinoma.

Sentinel lymph node biopsy (SLNB) is a diagnostic staging procedure that aims to identify the first draining lymph node(s) from the primary tumor, the sentinel lymph nodes (SLN), as their histopathological status reflects the histopathological status of the rest of the nodal basin. The routine SLNB procedure consists of peritumoral injections with a technetium-99m [99mTc]-labelled radiotracer followed by lymphoscintigraphy and SPECT-CT imaging. Based on these imaging results, the identified SLNs are marked for surgical extirpation and are subjected to histopathological assessment. The routine SLNB procedure has proven to reliably stage the clinically negative neck in early-stage oral squamous cell carcinoma (OSCC). However, an infamous limitation arises in situations where SLNs are located in close vicinity of the tracer injection site. In these cases, the hotspot of the injection site can hide adjacent SLNs and hamper the discrimination between tracer injection site and SLNs (shine-through phenomenon). Therefore, technical developments are needed to bring the diagnostic accuracy of SLNB for early-stage OSCC to a higher level. This review evaluates novel SLNB imaging techniques for early-stage OSCC: MR lymphography, CT lymphography, PET lymphoscintigraphy and contrast-enhanced lymphosonography. Furthermore, their reported diagnostic accuracy is described and their relative merits, disadvantages and potential applications are outlined.