The added value of SPECT-CT for the identification of sentinel lymph nodes in early stage oral cancer.

PURPOSE: To assess the role of single-photon emission computed tomography with computed tomography (SPECT-CT) for the identification of sentinel lymph nodes (SLNs) in patients with early stage (T1-T2) oral cancer and a clinically negative neck (cN0). METHODS: In addition to planar lymphoscintigraphy, SPECT-CT was performed in 66 consecutive patients with early stage oral cancer and a clinically negative neck. The addition of SPECT-CT to planar images was retrospectively analyzed for the number of additional SLNs, more precise localization of SLNs, and importance of anatomical information by a team consisting of a nuclear physician, surgeon, and investigator. RESULTS: Identification rate for both imaging modalities combined was 98% (65/66). SPECT-CT identified 15 additional SLNs in 14 patients (22%). In 2/15 (13%) of these additional SLNs, the only metastasis was found, resulting in an upstaging rate of 3% (2/65). In 20% of the patients with at least one positive SLN, the only positive SLN was detected due to the addition of SPECT-CT. SPECT-CT was considered to add important anatomical information in two patients (3%). In 5/65 (8%) of the patients initially scored SLNs on planar lymphoscintigrams were scored as non-SLNs when SPECT-CT was added. There were four false-negative SLN biopsy procedures in this cohort. CONCLUSIONS: The addition of SPECT-CT to planar lymphoscintigraphy is recommended for the identification of more (positive) SLNs and better topographical orientation for surgery in sentinel lymph node biopsy for early stage oral cancer.

MIBG scans in patients with stage 4 neuroblastoma reveal two metastatic patterns, one is associated with MYCN amplification and in MYCN-amplified tumours correlates with a better prognosis.

PURPOSE: The aim of this study was to find clinically relevant MIBG-avid metastatic patterns in patients with newly diagnosed stage 4 neuroblastoma. METHODS: Diagnostic (123)I-MIBG scans from 249 patients (123 from a European and 126 from the COG cohort) were assessed for metastatic spread in 14 body segments and the form of the lesions: "focal" (clear margins distinguishable from adjacent background) or "diffuse" (indistinct margins, dispersed throughout the body segment). The total numbers of diffuse and focal lesions were recorded. Patients were then categorized as having lesions exclusively focal, lesions more focal than diffuse, lesions more diffuse than focal, or lesions exclusively diffuse. RESULTS: Diffuse lesions affected a median of seven body segments and focal lesions a median of two body segments (P < 0.001, both cohorts). Patients with a focal pattern had a median of 2 affected body segments and those with a diffuse pattern a median of 11 affected body segments (P < 0.001, both cohorts). Thus, two MIBG-avid metastatic patterns emerged: "limited-focal" and "extensive-diffuse". The median numbers of affected body segments in MYCN-amplified (MNA) tumours were 5 (European cohort) and 4 (COG cohort) compared to 9 and 11, respectively, in single-copy MYCN (MYCNsc) tumours (P < 0.001). Patients with exclusively focal metastases were more likely to have a MNA tumour (60% and 70%, respectively) than patients with the other types of metastases (23% and 28%, respectively; P < 0.001). In a multivariate Cox regression analysis, focal metastases were associated with a better event-free and overall survival than the other types of metastases in patients with MNA tumours in the COG cohort (P < 0.01). CONCLUSION: Two metastatic patterns were found: a "limited and focal" pattern found mainly in patients with MNA neuroblastoma that correlated with prognosis, and an "extensive and diffuse" pattern found mainly in patients with MYCNsc neuroblastoma.

Practice variation in defining sentinel lymph nodes on lymphoscintigrams in oral cancer patients.

PURPOSE: Lymphoscintigraphic imaging and adequate interpretation of the lymphatic drainage pattern is an essential step in the sentinel lymph node biopsy (SLNB) procedure. In oral cancer, identification of the sentinel lymph node (SLN) can be challenging. In this study, interobserver variability in defining SLNs on lymphoscintigrams was evaluated in patients with T1-T2 stage N0 oral cancer. METHODS: Sixteen observers (head and neck surgeons, nuclear medicine physicians or teams of both) from various institutes were asked which criteria they use to consider a hot focus on the lymphoscintigram as SLN. Lymphoscintigrams of 9 patients with 47 hot foci (3-9 per patient) were assessed, using a scale of 'yes/equivocal/no'. Bilateral drainage was seen in four of nine cases. In three cases additional late single photon emission computed tomography (SPECT)/CT scanning was performed. Interobserver variability was evaluated by kappa (к) analysis, using linear weighted pairwise comparison of the observers. Conservative (equivocal analysed as no) and sensitive (equivocal analysed as yes) assessment strategies were investigated using pairwise kappa analysis. RESULTS: Various definitions of SLN on lymphoscintigrams were given. Interobserver variability of all cases using a 3-point scale showed fair agreement (71%, к(w) = 0.29). The conservative and sensitive analyses both showed moderate agreement: conservative approach к = 0.44 (in 80% of the hot foci the observers agreed) and sensitive approach к = 0.42 (81%) respectively. Multidisciplinary involvement in image interpretation and higher levels of observer experience appeared to increase agreement. CONCLUSION: Among 16 observers, there is practice variation in defining SLNs on lymphoscintigrams in oral cancer patients. Interobserver variability of lymphoscintigraphic interpretation shows moderate agreement. In order to achieve better agreement in defining SLNs on lymphoscintigrams specific guidelines are warranted.

When Limb Surgery Has Become the Only Life-Saving Therapy in FOP: A Case Report and Systematic Review of the Literature.

Fibrodysplasia ossificans progressiva (FOP) is a rare disease in which heterotopic ossification (HO) is formed in muscles, tendons and ligaments. Traumatic events, including surgery, are discouraged as this is known to trigger a flare-up with risk of subsequent HO. Anesthetic management for patients with FOP is challenging. Cervical spine fusion, ankylosis of the temporomandibular joints, thoracic insufficiency syndrome, restrictive chest wall disease, and sensitivity to oral trauma complicate airway management and anesthesia and pose life-threatening risks. We report a patient with FOP suffering from life-threatening antibiotic resistant bacterial infected ulcers of the right lower leg and foot. The anesthetic, surgical and postoperative challenges and considerations are discussed. In addition, the literature on limb surgeries of FOP patients is systemically reviewed. The 44 year-old female patient was scheduled for a through-knee amputation. Airway and pulmonary evaluation elicited severe abnormalities, rendering standard general anesthesia a rather complication-prone approach in this patient. Thus, regional anesthesia, supplemented with intravenous analgosedation and N2O-inhalation were performed in this case. The surgery itself was securely planned to avoid any unnecessary tissue damage. Postoperatively the patient was closely monitored for FOP activity by ultrasound and [18F]PET/CT-scan. One year after surgery, a non-significant amount of HO had formed at the operated site. The systematic review revealed seventeen articles in which thirty-two limb surgeries in FOP patients were described. HO reoccurrence was described in 90% of the cases. Clinical improvement due to improved mobility of the operated joint was noted in 16% of the cases. It should be noted, though, that follow-up time was limited and no or inadequate imaging modalities were used to follow-up in the majority of these cases. To conclude, if medically urgent, limb surgery in FOP is possible even when general anesthesia is not preferred. The procedure should be well-planned, alternative techniques or procedures should be tested prior to surgery and special attention should be paid to the correct positioning of the patient. According to the literature recurrent HO should be expected after surgery of a limb, even though it was limited in the case described.

Acquisition settings for PET of 124I administered simultaneously with therapeutic amounts of 131I.

UNLABELLED: Radiation dosimetry of thyroid cancer therapy with 131I can be performed by coadministration of 124I followed by longitudinal PET scans over several days. The photons emitted by 131I may affect PET image quality. The aim of this study was to assess the influence of large amounts of 131I on PET image quality and accuracy with various acquisition settings. METHODS: Noise equivalent count (NEC) rates of 124I only were measured with a standard clinical PET scanner. Apart from the standard 350- to 650-keV energy window, 425- to 650-keV and 460- to 562-keV windows were used and data were acquired both with (2-dimensional) and without (3-dimensional [3D]) septa. A phantom containing 6 hot spheres, filled with a combination of 131I and 124I and with a sphere-to-background ratio of 18:1, was scanned repeatedly with energy window settings as indicated and emission and transmission scan durations of 7 and 3 min, respectively. NEC rates were calculated and compared with those measured with the phantom filled with only 124I. Sphere-to-background ratios in the reconstructed images were determined. One patient with known metastatic thyroid cancer was scanned using energy window settings and scan times as indicated 3 and 6 d after administration of 5.5 GBq of 131I and 75 MBq of 124I. RESULTS: The highest 124I-only NEC rates were obtained using a 425- to 650-keV energy window in 3D mode. In the presence of (131)I, the settings giving the highest NEC rate and contrast were 425-650 keV and 460-562 keV in 3D mode, with the clinical scans giving the highest quality images with the same settings. CONCLUSION: Acquisition in 3D mode with a 425- to 650-keV or 460- to 562-keV window leads to the highest image quality and contrast when imaging 124I in the presence of large amounts of 131I using a standard clinical PET scanner.

Two tissue-resident progenitor lineages drive distinct phenotypes of heterotopic ossification.

Fibrodysplasia ossificans progressiva (FOP), a congenital heterotopic ossification (HO) syndrome caused by gain-of-function mutations of bone morphogenetic protein (BMP) type I receptor ACVR1, manifests with progressive ossification of skeletal muscles, tendons, ligaments, and joints. In this disease, HO can occur in discrete flares, often triggered by injury or inflammation, or may progress incrementally without identified triggers. Mice harboring an Acvr1R206H knock-in allele recapitulate the phenotypic spectrum of FOP, including injury-responsive intramuscular HO and spontaneous articular, tendon, and ligament ossification. The cells that drive HO in these diverse tissues can be compartmentalized into two lineages: an Scx+ tendon-derived progenitor that mediates endochondral HO of ligaments and joints without exogenous injury, and a muscle-resident interstitial Mx1+ population that mediates intramuscular, injury-dependent endochondral HO. Expression of Acvr1R206H in either lineage confers aberrant gain of BMP signaling and chondrogenic differentiation in response to activin A and gives rise to mutation-expressing hypertrophic chondrocytes in HO lesions. Compared to Acvr1R206H, expression of the man-made, ligand-independent ACVR1Q207D mutation accelerates and increases the penetrance of all observed phenotypes, but does not abrogate the need for antecedent injury in muscle HO, demonstrating the need for an injury factor in addition to enhanced BMP signaling. Both injury-dependent intramuscular and spontaneous ligament HO in Acvr1R206H knock-in mice were effectively controlled by the selective ACVR1 inhibitor LDN-212854. Thus, diverse phenotypes of HO found in FOP are rooted in cell-autonomous effects of dysregulated ACVR1 signaling in nonoverlapping tissue-resident progenitor pools that may be addressed by systemic therapy or by modulating injury-mediated factors involved in their local recruitment.

Sentinel node biopsy for early-stage oral cavity cancer: the VU University Medical Center experience.

BACKGROUND: Sentinel node biopsy (SNB) in head and neck cancer is recently introduced as the staging technique of oral squamous cell carcinoma. We report the results of SNB in patients diagnosed with a T1-T2 oral squamous cell carcinoma and clinically negative (N0) neck in a single center. METHODS: A retrospective analysis of 90 previously untreated patients who underwent SNB between 2007 and 2012 was performed. The SNB procedure consisted of preoperatively performed lymphoscintigraphy, intraoperative detection using blue dye, and gamma probe guidance and histopathologic examination including step-serial sectioning (SSS) and immunohistochemical (IHC) staining. A positive SNB was followed by neck dissection, whereas regular follow-up with ultrasound-guided fine-needle aspiration cytology (FNAC) was done in case of a negative SNB. RESULTS: The lymphoscintigraphic identification rate was 98% (88 of 90 patients) and the surgical detection rate was 99% (87 of 88 patients). The upstaging rate was 30%. Sensitivity of SNB was 93% and the negative predictive value was 97%. The median follow-up was 18 months (range, 2-62 months). Overall survival (OS) and disease-free survival (DFS) for SNB negative were 100% and 84% and for SNB positive patients 73% and 88%, respectively. CONCLUSION: SNB is a reliable diagnostic staging technique for the clinically negative neck in patients with early-stage (T1-T2, cN0) oral squamous cell carcinoma.

Sentinel node identification in laryngeal cancer: Feasible in primary cancer with previously untreated neck.

OBJECTIVES: With the current diagnostic techniques a considerable percentage of occult lymph node metastases are missed in the clinically negative (cN0) neck. Therefore, in patients with laryngeal cancer and cN0 neck a total laryngectomy is usually combined with elective neck dissection. Based on the risk of occult lymph node metastases the decision whether to perform a neck dissection or not is difficult. In recurrent laryngeal cancer or second primary tumors previous treatment possibly influences lymphatics and metastatic behavior. In this pilot study we investigated the feasibility of sentinel node (SN) identification and potential accuracy of sentinel node biopsy (SNB) in laryngeal cancer patients undergoing total laryngectomy with elective neck dissection. PATIENTS AND METHODS: Patients with cN0 laryngeal cancer were included. During surgery 40MBq (99m)Technetium labeled Nanocolloid was endoscopically injected around the tumor. Lymphoscintigraphy was not performed. We identified the sentinel node (SN) ex vivo in the neck dissection specimen with a gammaprobe. Histopathological examination of the neck dissection specimen served as reference test. RESULTS: We included 19 patients, 13 patients with untreated necks and six with prior neck treatment. SN identification was successful in 68.4% (13/19) of patients, and significantly higher in patients with untreated necks (92.3% versus 16.7%, p<0.01). Four of 13 (30.7%) patients would potentially be upstaged by SNB. Sensitivity and negative predictive value would have been 80.0% and 87.5%, respectively. CONCLUSION: With the current methodology, SN identification in laryngeal cancer patients undergoing total laryngectomy is feasible in patients with untreated necks. Further studies are needed to determine the exact accuracy of SNB in total laryngectomy patients.

Pilot study on the feasibility of PET/CT lymphoscintigraphy with 89Zr-nanocolloidal albumin for sentinel node identification in oral cancer patients.

UNLABELLED: With conventional imaging techniques such as planar lymphoscintigraphy and SPECT/CT, preoperative sentinel node (SN) identification can be difficult when the SN is near the primary tumor, as is the case in floor-of-mouth carcinomas. PET/CT lymphoscintigraphy may improve the detection and localization of such SNs. METHODS: In this study, the clinical feasibility of PET/CT lymphoscintigraphy using (89)Zr-nanocolloidal albumin was evaluated in 5 oral cancer patients. PET/CT lymphoscintigraphy was performed after peritumoral injection of (89)Zr-nanocolloidal albumin. The routine SN procedure, including SPECT/CT using (99m)Tc-nanocolloidal albumin, was performed on the same patients 7-9 d after the injection of (89)Zr-nanocolloidal albumin. RESULTS: Comparison of radiocolloid distribution on PET/CT and SPECT/CT showed identical drainage patterns. Moreover, PET/CT was able to identify additional foci near the primary tumor. CONCLUSION: This pilot PET/CT study on SN detection indicated that lymphoscintigraphy using (89)Zr-nanocolloidal albumin is feasible.

Sentinel node biopsy for oral and oropharyngeal squamous cell carcinoma in the previously treated neck.

In patients with early stage oral or oropharyngeal squamous cell carcinoma (OSCC) sentinel node biopsy (SNB) is a reliable method to detect occult disease in the neck. However, patients with a history of surgery or radiotherapy in the neck may have aberrant lymphatic drainage caused by disruption of lymphatic channels. Therefore, treatment of the same levels at risk as in the primary setting may not be appropriate. The aim of our prospective observational study was to evaluate the clinical application of SNB in previously treated OSCC. Between 2003 and 2010 twenty-two patients were included. Lymph node mapping consisted of preoperative lymphoscintigraphy, SPECT/CT, intraoperative use of gamma-probe and patent blue. Endpoints were the sentinel node (SN) detection rate, unexpected lymphatic drainage patterns, negative predictive value and regional tumor control. 4/22 (18%) Patients were previously treated only on the contralateral site. The SN detection rate was 100% and unexpected drainage was found in 1/4 patients. The other 18 patients had ipsi- or bilateral previous neck treatment and a SN detection rate of 83%. The upstaging rate was 7% and 67% had unexpected lymphatic drainage patterns. The median follow-up was 22 months. Regional tumor control and negative predictive value were 100%. SNB in previously treated OSCC patients is feasible. SN detection is reliable and regional tumor control after staging by SNB is excellent. Moreover, SNB renders an assessment of the individual lymphatic drainage pattern, compensating for a potential variability after previous treatment of the neck.

Visualization of the sentinel node in early-stage oral cancer: limited value of late static lymphoscintigraphy.

OBJECTIVE: Various lymphoscintigraphic imaging protocols exist for sentinel node (SN) identification in early-stage oral cancer. This study aimed to evaluate the clinical value of performing additional late lymphoscintigraphic imaging. METHODS: We retrospectively analysed early (directly following injection of 99mTc-Nanocoll) and late (2-4 h after injection) imaging results of 60 early-stage (T1-T2, cN0) oral cancer patients scheduled for SN procedure. Lymphoscintigraphic results of late imaging were categorized into: (a) no visualization of additional hotspots considered to be SNs; (b) additional hotspots visualized that are considered to be SNs and (c) hotspots visualized only during late imaging. Histopathological results of the harvested SNs were related to the corresponding hotspot. RESULTS: In all patients (n=60) lymphoscintigraphy was able to visualize a hotspot that was identified as an SN. In 51/60 (85%) patients, early imaging was able to visualize at least one hotspot, whereas in 9/60 (15%) patients, mostly with oral cavity tumours other than mobile tongue and floor-of-mouth tumours, only late imaging was able to visualize hotspots. In 14/51 (27%) patients, late imaging resulted in additionally visualized hotspots marked as SNs, resulting in a more extensive surgical procedure. These additionally removed SNs appeared to be of no clinical relevance, as all SNs identified during early imaging correctly predicted whether the neck was positive or negative for cancer. CONCLUSION: Results of this study indicate that additional late lymphoscintigraphic imaging should be performed only in selected cases.

Gastric emptying, glucose metabolism and gut hormones: evaluation of a common preoperative carbohydrate beverage.

OBJECTIVE: To study the gastric-emptying rate and gut hormonal response of two carbohydrate-rich beverages. A specifically designed carbohydrate-rich beverage is currently used to support the surgical patient metabolically. Fruit-based beverages may also promote recovery, due to natural antioxidant and carbohydrate content. However, gastric emptying of fluids is influenced by its nutrient composition; hence, safety of preoperative carbohydrate loading should be confirmed. Because gut hormones link carbohydrate metabolism and gastric emptying, hormonal responses were studied. METHODS: In eight volunteers, gastric emptying rates of both 400 mL of a ready-to-use beverage (A: Nutricia preOp; 50.4 g carbohydrates-mainly polysaccharides; 260 mOsm/kg) and 400 mL over-the-counter fruit-based lemonade (B: Roosvicee Original; 48 g carbohydrates--mainly fruit-associated saccharides; 805 mOsm/kg) were determined scintigraphically (using hepatate Tc-99(m)) according to a crossover design. Plasma glucose, insulin, C-peptide, glucagon-like peptide (GLP-1), peptide YY, total glucagon, and ghrelin were studied. RESULTS: Gastric emptying showed no differences in residual volumes. Earlier onset in emptying for beverage A versus B was observed (trend), with significantly higher glucose, insulin, C-peptide, and glucagon responses at 15-90 min. GLP-1 was inversely related to residual volume. CONCLUSION: Fruit-based lemonade is a safe alternative for preoperative purposes. It induces a more limited glucose, insulin, and C-peptide response. Later onset in gastric emptying (B versus A: trend), lower glucagon release, and differences in beverage content and osmolarity may have contributed to those differences. Efficient emptying was reflected by early GLP-1 levels.

The value of nuclear scans in cochlear implant infections.

We discuss the diagnostic value of nuclear scintigraphy in the management of infections after cochlear implantation. A 56-year-old female (Case 1) and a 46-year-old female (Case 2) developed complaints of diffuse headache, 4 and 5 months after cochlear implantation, without other signs of infection during examination, laboratorial testing and initial computed tomography. In Case 1 we performed a technetium 99 m-difosfate scintigraphy, which showed an increased uptake in the right petrosal bone, suggestive of chronic osteomyelitis. This case failed conservative treatment and underwent complete explantation, after which 67gallium-citrate single-photon emission computed tomography normalized during follow-up. In Case 2 inflammation at the site of the cochlear implant was confirmed by performing a positron emission tomography scan, which showed an increased uptake. Case 2 was treated successfully with antibiotics. Both have no signs of recurrent infection. Nuclear scintigraphy can be the single valuable tool in case of a late low-grade infection after cochlear implantation. Delayed low-grade chronic osteomyelitis of the petrosal bone is a rare but dramatic complication after cochlear implantation. It can develop with minimal signs of infection.