Evidence for a Better Nodal Staging System for Melanoma: The Clinical Relevance of Metastatic Disease Confined to the Sentinel Lymph Nodes

Background

The hypothesis tested in this study was whether patients with stage III metastatic melanoma confined to their sentinel lymph nodes (SLNs) had a more favorable prognosis than patients who had SLN and non-SLN (NSLN) metastases.

Methods

Patients were identified who were clinically negative in their regional basins but with lymphatic mapping were found to have positive SLNs (331 patients). All patients subsequently underwent a complete lymph node dissection of the lymphatic basin involved, and the total number of metastatic SLNs and NSLNs were documented.

Results

As the regional metastatic disease involves NSLNs, disease-free survival (DFS) and overall survival (OS) decreases. For patients with a total of 2 nodes positive, those with disease confined to the SLNs had a significant better prognosis (DFS and OS: P < .00001) than those in whom 1 SLN and 1 non-SLN was involved. This difference was apparent for those patients with N2 and N3 disease (2 or more nodes positive in their regional basin). A multivariate regression analysis that included Breslow thickness, ulceration, number of positive nodes, and NSLN positivity showed that NSLN positivity (P = .0019) was the most powerful predictor of DFS and OS.

Conclusions

When metastatic melanoma overwhelms the SLN and involves NSLNs, the biologic behavior changes to portend a worse survival, regardless of the total node count positive. These data make the argument that the current N staging system should be changed to incorporate SLN vs NSLN involvement.     

Failure of urethane anesthetic to block induction of pineal serotonin N-acetyltransferase activity in the rat

SHIVERS, B. D. Failure of urethane anesthetic to block induction of pineal serotonin N-acetyltransferase activity in therat. BRAIN RES. BULL. 3(6) 579–581, 1978.—Ability of urethane anesthetic to block induction of pineal serotonin N-acetyltransferase (SNAT; E.C.2.3.1.5) activity was measured in individual rat pineal glands in animals receiving urethane (25% w/v, IP, 1.2 g/kg) or saline, 6 hr prior to sacrifice. Using a radioenzymatic assay, SNAT determinations were made twice daily (at 1200 or 2400 hr) immediately after the sacrifice of each animal. The results show that urethane had no effect on the induction of SNAT activity: (1) implying that the neural activity of those structures involved in induction of SNAT activity (e.g., suprachiasmatic nucleus) is not substantially altered by this anesthetic and (2) suggesting that the central blockade of ovulation by urethane does not include alterations in suprachiasmatic nucleus activity.     

Molecular staging for melanoma and breast cancer.

Despite increased sensitivity of PCR techniques, routine H&E histology and, in some cases, immunohistochemistry remain the gold standards for the detection of micrometastatic disease. Highly sensitive and specific molecular assays such as RT-PCR provide an ideal way to detect micrometastatic disease in tissues or blood at risk for metastases. RT-PCR has been shown to increase detection of micrometastases, especially in patients with breast cancer and melanoma. These assays have the potential to provide valuable tumor staging and progression information and thus determine the need for further surgery, adjuvant chemotherapy, and antigen-specific immunotherapy. As investigators gain more experience using molecular assays, the results of these assays will be more likely to guide clinical staging and decision making.     

Freeze-fracture analysis of intramembrane particles of erythrocytes from normal and dystrophic hamsters

The intramembrane particles on plasma membranes of erythrocytes of Syrian hamsters afflicted with hereditary muscular dystrophy were compared to those from normal controls by freeze-fracture analysis. The reduced number of particles in both fracture faces of dystrophic erythrocyte plasmalemmae, as compared to that of control red cells, was found to be highly significant (P = .001). Results of this study therefore, support the concept of a generalized membrane defect (abnormality) in muscular dystrophy.     

Haloperidol increases proenkephalin mRNA levels in the caudate-putamen of the rat: a quantitative study at the cellular level using in situ hybridization

Previous immunocytochemical studies have shown that the opioid peptides, Met-enkephalin and Leu-enkephalin, are present in medium-sized, spiny projection neurons of the caudate-putamen. It has also been demonstrated that chronic treatment of rats with the dopamine receptor blocker, haloperidol, results in an increase in the levels of enkephalin peptides and proenkephalin mRNA in this brain region. To determine whether this increase in proenkephalin mRNA content is exhibited by all enkephalinergic neurons of the caudate-putamen or by only a subpopulation, we have used in situ nucleic acid hybridization to examine the haloperidol-induced increase in proenkephalin mRNA levels at the cellular level. Results of in situ hybridization suggest that all enkephalinergic neurons in the caudate-putamen can respond to haloperidol treatment with an increase in steady state levels of proenkephalin mRNA, and that the mean induction is an approximate 3-fold increase in the message levels. This suggests that dopamine exerts a tonic inhibitory effect on the expression of the proenkephalin gene in all of the enkephalinergic neurons of the caudate-putamen. Dot blot analysis indicated a 2.4-fold increase in the tissue levels of this mRNA. The agreement between the in situ hybridization results and dot blot analysis supports in situ hybridization as a reliable method for quantitative studies of alterations in neuropeptide precursor mRNAs in the brain.     

“Turn It Off!”: Diabetes Device Alarm Fatigue Considerations for the Present and the Future

Safe and widespread use of diabetes technology is constrained by alarm fatigue: when someone receives so many alarms that he or she becomes less likely to respond appropriately. Alarm fatigue and related usability issues deserve consideration at every stage of alarm system design, especially as new technologies expand the potential number and complexity of alarms. The guiding principle should be patient wellbeing, while taking into consideration the regulatory and liability issues that sometimes contribute to building excessive alarms. With examples from diabetes devices, we illustrate two complementary frameworks for alarm design: a “patient safety first” perspective and a focus on human factors. We also describe opportunities and challenges that will come with new technologies such as remote monitoring, adaptive alarms, and ever-closer integration of glucose sensing with insulin delivery.     

Dynamics of C6 Astrocytoma Invasion into Three-dimensional Collagen Gels

Objective: The dynamic mechanisms underlying the three-dimensional invasive paradigm of C₆ astrocytoma cells has been assessed.Methods: Spheroids of C₆ astrocytoma cells were implanted into three-dimensional collagen type I gels (vitrogen 100) and individual C₆ astrocytoma cell invasion monitored. Time-lapsed videomicroscopy was used to assess the dynamic components of cell invasion in three dimensions while scanning and transmission electron microscopy were used to assess matrix architecture and the static aspects of cell invasion.Results: Videomicroscopy outlined an invasion paradigm continuum with repeating phases. A cell surface ruffling phase was followed by invadopodia extension and pull up phases. For some cells the collagen type I matrix extracellular matrix appeared to modify the ability of C₆ cells to carry out their invasion paradigm.Conclusions: C₆ astrocytoma cells invading a three-dimensional collagen type I matrix utilize a invasion paradigm made up of a number of phases. A better understanding of the dynamic invasion paradigms of malignant glial cells may be useful in the development of effective treatment strategies to prevent or modify malignant glioma invasion.