Malignant peripheral nerve sheath tumors of the head and neck: A clinicopathological study

Twenty-seven cases of malignant peripheral nerve sheath tumors involving the head and neck region over a period of 7 years were reviewed. They were graded from 1–3 based on necrosis, mitosis, cellularity, and pleomor-phism. Mean age of occurrence was 42 years, with a range of 12–70 years. Male preponderance was noted (M:F = 3.5:1). The most common site of involvement was the neck (44.6%). The main presenting symptom was an enlarging mass. The nerve of origin could be identified in 33% of patients. Treatment consisted of wide excision. The 5-year observed survival was 33%. Fifty-two percent of patients developed local recurrence of disease. Fifteen percent of patients died due to advanced local disease within 18 months of treatment. Distant metastasis was seen in 18.5% of patients. Lymph node metastasis was not seen. At the end of 5 years 15% of patients remained disease free. Large tumor size (>5 cm) adversely affected the prognosis (P = < 0.1). No significant correlation was noted between the grade of tumor and survival. © Wiley-Liss, Inc.     

Perioperative and ICU Healthcare Analytics within a Veterans Integrated System Network: a Qualitative Gap Analysis

Health care facilities are implementing analytics platforms as a way to document quality of care. However, few gap analyses exist on platforms specifically designed for patients treated in the Operating Room, Post-Anesthesia Care Unit, and Intensive Care Unit (ICU). As part of a quality improvement effort, we undertook a gap analysis of an existing analytics platform within the Veterans Healthcare Administration. The objectives were to identify themes associated with 1) current clinical use cases and stakeholder needs; 2) information flow and pain points; and 3) recommendations for future analytics development. Methods consisted of semi-structured interviews in 2 phases with a diverse set (n = 9) of support personnel and end users from five facilities across a Veterans Integrated Service Network. Phase 1 identified underlying needs and previous experiences with the analytics platform across various roles and operational responsibilities. Phase 2 validated preliminary feedback, lessons learned, and recommendations for improvement. Emerging themes suggested that the existing system met a small pool of national reporting requirements. However, pain points were identified with accessing data in several information system silos and performing multiple manual validation steps of data content. Notable recommendations included enhancing systems integration to create “one-stop shopping” for data, and developing a capability to perform trends analysis. Our gap analysis suggests that analytics platforms designed for surgical and ICU patients should employ approaches similar to those being used for primary care patients.     

Preclinical evaluation for noninvasive reversal following long-term vas occlusion with styrene maleic anhydride in langur monkeys

A preclinical evaluation for reversal through a noninvasive approach following long-term vas occlusion with styrene maleic anhydride (SMA) has been attempted in langur monkeys at the level of semen parameters, sperm functional tests, semen biochemistry, histology and ultrastructure of reproductive organs, hematology and serum clinical biochemistry including antisperm antibodies (ASA), prostate-specific antigen (PSA) and testosterone. Noninvasive reversal through palpation, percutaneous squeezing and electrical stimulation, forced vibratory movements and suprapubic percussion in the inguinal segments and per-rectal digital massage was attempted in seven langur monkeys after 540 days following vas occlusion. The results revealed instant azoospermia reversal on the same day of reversal with impaired sperm quality, which showed gradual improvement and normospermia with normal motility and viability after 60-90 days of reversal. Sperm functional tests, including ultrastructure of spermatozoa, indicative of sterility in the initial ejaculations, reached normalcy after 90-120 days of reversal. The seminal plasma biochemistry indicative of obstructive azoospermia regained a normal pattern after 90-120 days of reversal. The morphology of testes that showed focal degeneration during 540 days of vas occlusion and that of vasa deferentia that showed exfoliation of epithelial cells resumed to normal morphology comparable with control animals after 150 days of reversal. The morphology of the epididymis, seminal vesicle and prostate did not show appreciable changes following vas occlusion and after noninvasive reversal compared with those of control animals. Hematology, serum clinical chemistry, ASA, PSA and testosterone fluctuated within control limits, indicating safety of the procedure at the level of accessory reproductive organs. The results suggest that noninvasive reversal is feasible even after long-term vas occlusion with SMA and is safe without adverse side effects.     

Loss of heterozygosity mapping at chromosome arm 16q in 712 breast tumors reveals factors that influence delineation of candidate regions

Loss of heterozygosity (LOH) at the long arm of chromosome 16 occurs in at least half of all breast tumors and is considered to target one or more tumor suppressor genes. Despite extensive studies by us and by others, a clear consensus of the boundaries of the smallest region of overlap (SRO) could not be identified. To find more solid evidence for SROs, we tested a large series of 712 breast tumors for LOH at 16q using a dense map of polymorphic markers. Strict criteria for LOH and retention were applied, and results that did not meet these criteria were excluded from the analysis. We compared LOH results obtained from samples with different DNA isolation methods, ie., from microdissected tissue versus total tissue blocks. In the latter group, 16% of the cases were excluded because of noninterpretable LOH results. The selection of polymorphic markers is clearly influencing the LOH pattern because a chromosomal region seems more frequently involved in LOH when many markers from this region are used. The LOH detection method, i.e., radioactive versus fluorescence detection, has no marked effect on the results. Increasing the threshold window for retention of heterozygosity resulted in significantly more cases with complex LOH, i.e., several alternating regions of loss and retention, than seen in tumors with a small window for retention. Tumors with complex LOH do not provide evidence for clear-cut SROs that are repeatedly found in other samples. On disregarding these complex cases, we could identify three different SROs, two at band 16q24.3 and one at 16q22.1. In all three tumor series, we found cases with single LOH regions that designated the distal region at 16q24.3 and the region at 16q22.1. Comparing histological data on these tumors did not result in the identification of a particular subtype with LOH at 16q or a specific region involved in LOH. Only the rare mucinous tumors had no 16q LOH at all. Furthermore, a positive estrogen content is prevalent in tumors with 16q LOH, but not in tumors with LOH at 16q24.3 only.     

Regulation of motility,invasion, and metastatic potential of squamous cell carcinoma by 1α,25‐dihydroxycholecalciferol

BACKGROUND:

The active metabolite of vitamin D 1α,25‐dihydroxycholecalciferol (1,25D₃) has exhibited broad‐spectrum antitumor activity in xenograft animal models. However, its activity against metastatic disease has not been extensively investigated.

METHODS:

Squamous cell carcinoma (SCC) or 1,25D₃‐resistant variant SCC‐DR cells were treated with 1,25D₃. Actin organization was examined by immunofluorescence assay. Cell migration was assessed by “wound” healing and chemotactic migration assays. Cell invasion was assessed by a Matrigel‐based invasion assay and in situ zymography. Matrix metalloproteinase 2 (MMP‐2) and MMP‐9 expression and secretion were examined by immunoblot analysis and an enzyme‐linked immunosorbent assay, respectively. E‐cadherin expression was assessed by flow cytometry, immunoblot analysis, and immunohistochemistry. Knockdown of E‐cadherin was achieved by small interfering RNA. An experimental metastasis mouse model was created by intravenous injection of tumor cells; and lung tumor development in the mice was assessed by magnetic resonance imaging, gross observation, and histology.

RESULTS:

SCC cellular morphology and actin organization were altered by 10 nM 1,25D₃. 1,25D₃ inhibited SCC cell motility and invasion, which were associated with reduced expression and secretion of MMP‐2 and MMP‐9, and 1,25D₃ promoted the expression of E‐cadherin. These findings were not observed in SCC‐DR cells. Knock down of E‐cadherin rescued 1,25D₃‐inhibited cell migration. Intravenous injection of SCC or SCC‐DR cells resulted in the establishment of extensive pulmonary lesions in saline‐treated C3H mice. Treatment with 1,25D₃ resulted in a marked reduction in the formation of lung tumor colonies in mice that were injected with SCC cells, but not in mice that were injected with SCC‐DR cells.

CONCLUSIONS:

1,25D₃ suppressed SCC cell motility, invasion, and metastasis, partially through the promotion of E‐cadherin‐mediated cell‐cell adhesion. Cancer 2013. © 2012 American Cancer Society.