How many sentinel nodes should be harvested in oral squamous cell carcinoma?

The number of harvested lymph nodes when performing sentinel lymph node (SLN) biopsy remains controversial. The aim of this study was to examine the maximum number of nodes to be harvested for histopathological analysis. We also wanted to determine if the level of radioactivity within a SLN or its size were indicators for the likelihood of nodal metastases. The SLNs from 34 neck dissection specimens from patients with T1/T2 N0 oral and oropharyngeal carcinomas were included. Altogether 76 SLNs were measured for radioactivity and lymph node dimensions and volume. Tumour was identified in 16 of 76 nodes (positive nodes), and the remaining 60 nodes were free from tumour (negative nodes). In 9 of 16 cases, metastases were in the hottest node. Two patients had more than one positive SLN: the first and fourth hottest in one and the second and fourth hottest nodes in another contained tumour. However, all patients would have been staged accurately if only the hottest three sentinel nodes had been retrieved. Lymph nodes that contained tumour had a greater maximum diameter than non-metastatic SLNs. To stage the neck accurately, only the three hottest lymph nodes required sampling

Prognostic factors in solitary plasmacytoma of the bone: a multicenter Rare Cancer Network study

BACKGROUND: Solitary plasmacytoma (SP) of the bone is a rare plasma-cell neoplasm. There are no conclusive data in the literature on the optimal radiation therapy (RT) dose in SP. Therefore, in this large retrospective study, we wanted to assess the outcome, prognostic factors, and the optimal RT dose in patients with SP. METHODS: Data from 206 patients with bone SP without evidence of multiple myeloma (MM) were collected. Histopathological diagnosis was obtained for all patients. The majority (n = 169) of the patients received RT alone; 32 chemotherapy and RT, and 5 surgery. Median follow-up was 54 months (7–245). RESULTS: Five-year overall survival, disease-free survival (DFS), and local control was 70%, 46%, and 88%; respectively. Median time to MM development was 21 months (2–135) with a 5-year probability of 51%. In multivariate analyses, favorable factors were younger age and tumor size < 5 cm for survival; younger age for DFS; anatomic localization (vertebra vs. other) for local control. Older age was the only predictor for MM. There was no dose-response relationship for doses 30 Gy or higher, even for larger tumors. CONCLUSION: Younger patients, especially those with vertebral localization have the best outcome when treated with moderate-dose RT. Progression to MM remains the main problem. Further investigation should focus on adjuvant chemotherapy and/or novel therapeutic agents

Tauopathic Changes in the Striatum of A53T α-Synuclein Mutant Mouse Model of Parkinson's Disease

Tauopathic pathways lead to degenerative changes in Alzheimer's disease and there is evidence that they are also involved in the neurodegenerative pathology of Parkinson's disease [PD]. We have examined tauopathic changes in striatum of the α-synuclein (α-Syn) A53T mutant mouse. Elevated levels of α-Syn were observed in striatum of the adult A53T α-Syn mice. This was accompanied by increases in hyperphosphorylated Tau [p-Tau], phosphorylated at Ser202, Ser262 and Ser396/404, which are the same toxic sites also seen in Alzheimer's disease. There was an increase in active p-GSK-3β, hyperphosphorylated at Tyr216, a major and primary kinase known to phosphorylate Tau at multiple sites. The sites of hyperphosphorylation of Tau in the A53T mutant mice were similar to those seen in post-mortem striata from PD patients, attesting to their pathophysiological relevance. Increases in p-Tau were not due to alterations on protein phosphatases in either A53T mice or in human PD, suggesting lack of involvement of these proteins in tauopathy. Extraction of striata with Triton X-100 showed large increases in oligomeric forms of α-Syn suggesting that α-Syn had formed aggregates the mutant mice. In addition, increased levels of p-GSK-3β and pSer396/404 were also found associated with aggregated α-Syn. Differential solubilization to measure protein binding to cytoskeletal proteins demonstrated that p-Tau in the A53T mutant mouse were unbound to cytoskeletal proteins, consistent with dissociation of p-Tau from the microtubules upon hyperphosphorylation. Interestingly, α-Syn remained tightly bound to the cytoskeleton, while p-GSK-3β was seen in the cytoskeleton-free fractions. Immunohistochemical studies showed that α-Syn, pSer396/404 Tau and p-GSK-3β co-localized with one another and was aggregated and accumulated into large inclusion bodies, leading to cell death of Substantia nigral neurons. Together, these data demonstrate an elevated state of tauopathy in striata of the A53T α-Syn mutant mice, suggesting that tauopathy is a common feature of synucleinopathies

The Second International Conference on Sentinel Node Biopsy in Mucosal Head and Neck Cancer

Background: The Second International Conference on Sentinel Node Biopsy in Mucosal Head and Neck Cancer was hosted by the Department of Otorhinolaryngology, Head and Neck Surgery of the University Hospital in Zurich, Switzerland, from September 12 to 13, 2003. The aims of this conference were to present the results of validation studies and to achieve a consensus on methodological requirements. Methods: More than 80 delegates from 20 countries attended the conference. The presented validation studies were summarized and compared with the literature. Consensus was achieved concerning requirements for lymphatic mapping and histopathologic work-up. Results: Twenty centers presented results on 379 patients with cN0 disease. Sentinel nodes were identified in 366 (97%) of 379. Of these 366, 103 (29%) were positive for occult metastasis, and 263 (71%) were negative. Of those 263 patients, 11 patients (4%) showed nodal disease not revealed by the sentinel lymph node biopsy (SNB). The negative predictive value of a negative sentinel node for the remaining neck was 96%. The consensus conference resulted in the use of a radiotracer, lymphoscintigraphy, and a handheld gamma probe for lymphatic mapping as minimal requirements. The use of conventional hematoxylin and eosin staining and immunohistochemistry for cytokeratin is mandatory. Step-sectioning of the entire node at intervals of 150μm is recommended. Conclusions: The conference attracted delegates from all over the world, thus underscoring the high interest in the topic. With regard to the presented data and the data from the literature, SNB for early oral and oropharyngeal cancer is sufficiently validated. The consensus conference resulted in the definition of minimal methodological requirements for accurate SN