Faculty Bibliography

Hemangiopericytoma (HPC) is a rare vascular tumor arising from contractile cells around blood vessels, with the potential for malignant degeneration. Up to 10% of HPC occurs in children. Standard therapy for this tumor is surgical excision. We report the case of a 6-month-old infant with giant HPC involving the hand. Chemotherapy resulted in a decrease in tumor size, allowing for salvage of most of the hand and fingers. Preoperative chemotherapy should be considered in the care of HPC tumors involving the upper extremity in children

AIM: The objective of this study was to evaluate the early healing of endosseous implants presenting various healing chamber configurations in a beagle dog mandible model. METHODS: The four premolars of 12 beagle dogs were extracted and allowed to heal for a period of 8 weeks. Implants allowing six different healing chamber configurations were placed in each dog (three per side, six configurations per dog). The animals were sacrificed after 3 and 5 weeks in vivo (n=6 per time in vivo), and the implants were non-decalcified processed to slides of approximately 30 microm thickness. Bone-to-implant contact (BIC) and bone area fraction occupied (BAFO) within the healing chamber were quantified. Statistical analysis was performed by a GLM ANOVA model at 5% significance level. RESULTS: Osseointegration and healing with woven bone filling throughout all healing chambers was observed. Replacement of woven bone by lamellar bone showing primary osteonic structures was observed at 5 weeks. BIC was significantly affected by healing chamber configuration (P<0.001) and was not affected by time in vivo (P>0.42) at 3 and 5 weeks in vivo. BAFO was not affected by healing chamber configuration (P>0.14) however significantly increased over implantation time (P<0.001). CONCLUSION: Regardless of healing chamber design and dimensions considered, healing allowed the devices osseointegration. However, healing chamber configuration significantly affected osseointegration measurable parameters such as BIC.

Even though total absence of elbow flexion in obstetric brachial plexus palsy (OBPP) is rare, weakness is a frequent problem. Numerous procedures for elbow flexion restoration in late obstetric brachial plexus palsy have been described. In this study, children with OBPP who underwent secondary reconstruction for elbow flexion restoration were studied. A retrospective review of 15 patients (16 elbows) who underwent 16 pedicled and eight free-muscle transfers for elbow flexion restoration was conducted. The mean follow-up period was 8.4 +/- 2.9 years (range, 25 months to 12.2 years). The mean age at operation (elbow surgery) was 5.4 +/- 1.9 years. The total arc of elbow motion was the result of the active elbow flexion less the flexion contracture. There was significant improvement in biceps muscle power from an average grading of 2.49 +/- 0.80 preoperatively to 3.64 +/- 0.46 postoperatively (p < 0.001). Thirteen of 16 elbows (81%) achieved good and excellent results (>/=M3+); and three elbows (19%) fair results (M3- or M3). The average arc of motion was significantly improved from 36 degrees +/- 25 degrees preoperatively to 94 degrees +/- 26 degrees postoperatively (p < 0.001). The preoperative and postoperative average elbow flexion contracture was 10.9 degrees +/- 8.9 degrees and 20 degrees +/- 12.2 degrees , respectively. Pedicled and/or free-muscle transfers can significantly improve elbow flexion in late obstetric brachial plexus palsy. Choice of the procedure should be individualized and determined on the basis of the type of paralysis, availability of donor muscles, previous reconstruction, and experience of the surgeon.

The indications for free muscle transfer in brachial plexopathies are prolonged denervation time or inadequate upper extremity function after primary nerve reconstruction. The purpose of this study is to analyze the outcomes of free muscle transfer for elbow flexion and extension in brachial plexopathies in relation to the different muscles used and the respective motor donors. Seventy-three muscles were transferred for elbow flexion and ten for elbow extension. Latissimus dorsi (LD) was used in 37 cases, gracilis in 28, rectus femoris (RF) in seven, and vastus lateralis in one. Five LD and five gracilis were transferred for elbow extension. Patients younger than 15 years yielded better results than older patients for elbow flexion. When LD was transferred, the mean muscle grading (MG) was 3.33 +/- 0.25 when the neurotization was from intercostals; these outcomes were statistically significant when compared with outcomes of free gracilis transfer (MG 2.25 +/- 0.6). There was also a statistically significant difference when free LD was neurotized with three intercostals as compared with two intercostals nerves. RF yielded also good results when neurotized from contralateral C7 (cC7; MG 3.67 +/- 0.6). For elbow extension, the better outcomes of LD were not statistically significant. Among all the free muscle transfers for upper extremity reconstruction, elbow reanimation yielded the most rewarding outcomes. The selection of powerful muscle units was more important than the effect of neurotization which was not as strong as it was in muscle transfers for facial or hand reanimation

The purpose of this project was to study the effect of a subimmunosuppressive dose of FK506 (0.7 mg/kg per day) on nerve regeneration along a long nerve gap (4 cm), using the contralateral C7 nerve root transfer model for musculocutaneous nerve neurotization. Two types of tubes were applied to the nerve gap: a polycaprolactone tube and a collagen tube. Twenty adult male Sprague-Dawley rats were divided into 4 groups (n = 5). A polycaprolactone was used in groups 1 and 3 and a collagen tube in groups 2 and 4. Groups 1 and 2 were daily administered a subimmunosuppressive dose of FK506. Animals were euthanized on day 30. Evaluation consisted of behavioral assessment, needle electromyography studies, biceps muscle weight measurements, and qualitative and quantitative morphometry. Groups 1 and 2 showed higher mean values for fiber counts, axon diameters, myelin thickness and myelin area in C7, better functional evaluation results, and higher biceps weight left to right ratio than groups 3 and 4. There was no evidence of reinnervation potentials, and there were no axons detectable inside the tube lumen in any of the study groups. The present study demonstrated that there was nonsignificant improvement of the functional recovery, after systemic administration of a low dose of FK506. This was attributed to 3 factors: length of nerve gap; duration of follow up; and dose of FK506. However, FK506-treated animals tended to be in a more advanced stage of nerve regeneration compared with the control groups

The human homologue of the Drosophila segment polarity gene PTCH1, a tumor suppressor gene within the Sonic Hedgehog pathway has been implicated as the mutation responsible for nevoid basal cell carcinoma syndrome (NBCCS) as well as many other sporadic neoplasms. The calcifying epithelial odontogenic tumor (CEOT) is a rare and aggressive tumor of the jaws. The objective of this study was to investigate the role of the Sonic hedgehog pathway in the pathogenesis of the CEOT. We evaluated the protein distribution of PTCH and the transcription factors Gli1 and Gli2 within seven cases using immunohistochemistry. We also sought to confirm the findings by sequencing the PTCH1 gene from DNA extracted from the paraffin-embedded tissue of these cases. Seven cases of paraffin-embedded CEOT specimens were analyzed with immunohistochemistry. Immunoreactivity for Sonic hedgehog pathway proteins was evaluated using antibodies to the receptor PTCH as well as to the transcription factors Gli1 and Gli2. A keratocystic odontogenic tumor (KOT) from a 12year-old with NBCCS served as our positive control. Normal salivary gland tissue served as our negative control. PTCH gene sequencing was completed using PCR. Immunoreactivity to PTCH was seen in 6/7 cases, to Gli1 in 6/7 cases and to Gli2 in 6/7 cases. All three proteins were positive in the syndromic KOT and all proteins were negative in normal salivary tissue. Gene sequencing revealed five single-nucleotide polymorphisms (SNPs) of which two resulted in missense mutations. A missense mutation was also detected in the KOT. This study is the first to implicate the Sonic hedgehog pathway in the pathogenesis of the CEOT through sequencing. Similar to other odontogenic neoplasms gene mutations in PTCH1 are present in the CEOT

Endothelin-1 (ET-1) produced by various cancers is known to be responsible for inducing pain. While ET-1 binding to ETAR on peripheral nerves clearly mediates nociception, effects from binding to ETBR are less clear. The present study assessed the effects of ETBR activation and the role of endogenous opioid analgesia in carcinoma pain using an orthotopic cancer pain mouse model. mRNA expression analysis showed that ET-1 was nearly doubled while ETBR was significantly down-regulated in a human oral SCC cell line compared to normal oral keratinocytes (NOK). Squamous cell carcinoma (SCC) cell culture treated with an ETBR agonist (10(-4)M, 10(-5)M, and 10(-6) M BQ-3020) significantly increased the production of beta-endorphin without any effects on leu-enkephalin or dynorphin. Cancer inoculated in the hind paw of athymic mice with SCC induced significant pain, as indicated by reduction of paw withdrawal thresholds in response to mechanical stimulation, compared to sham-injected and NOK-injected groups. Intratumor administration of 3mg/kg BQ-3020 attenuated cancer pain by approximately 50% up to 3h post-injection compared to PBS-vehicle and contralateral injection, while intratumor ETBR antagonist BQ-788 treatment (100 and 300microg/kg and 3mg/kg) had no effects. Local naloxone methiodide (500microg/kg) or selective mu-opioid receptor antagonist (CTOP, 500microg/kg) injection reversed ETBR agonist-induced antinociception in cancer animals. We propose that these results demonstrate that peripheral ETBR agonism attenuates carcinoma pain by modulating beta-endorphins released from the SCC to act on peripheral opioid receptors found in the cancer microenvironment

BACKGROUND: Half of the patients with head and neck squamous cell carcinoma (HNSCC) can be expected to fail therapy, indicating that more aggressive treatment is warranted for this group. We have developed a novel risk model that can become a basis for developing new treatment paradigms. Here we report on the performance of our model in a new multicenter cohort. DESIGN: Eligible patients from 3 institutions (Montefiore Medical Center, University of Manitoba, and New York University Medical Center) were identified and pathology slides from their resection specimens were reviewed by Margaret Brandwein-Gensler; risk category was assigned as previously published. Kaplan-Meier analysis was performed for disease progression and survival. Cox proportional hazards regression was performed, adjusted for potential confounders. A teaching module was also developed; attending pathologists were asked to score coded slides after a lecture and multiheaded microscope teaching session. Agreement was assessed by calculating Cohen unweighted kappa coefficients. RESULT: The validation cohort consisted of 305 patients, from the above institutions, with 311 primary HNSCC of the oral cavity, oropharynx, and larynx. The median follow-up period for all patients was 27 months. Risk category predicts time to disease progression (P=0.0005), locoregional recurrence (P=0.013), and overall survival (P=0.0000) by Kaplan-Meier analysis. High-risk status is significantly associated with decreased time to disease progression, adjusted for clinical confounders (P=0.015, hazard ratio 2.32, 95% confidence interval 1.18-4.58) compared with collapsed intermediate and low-risk groups. We also demonstrate substantial interrater agreement (kappa=0.64), and very good rater agreement when compared with the standard (kappa=0.87). CONCLUSIONS: We demonstrate significant predictive performance of the risk model in a new cohort of patients with primary HNSCC, adjusted for confounders. Our training experience also supports the feasibility of adapting the risk model in clinical practice