Elbert T. Cheng

Simultaneous treatment with BDNF and CNTF after peripheral nerve transection and repair enhances rate of functional recovery compared with BDNF treatment alone

The objective was to investigate the effects of brain‐derived neurotropic factor (BDNF) and ciliary neurotropic factor (CNTF) on peripheral nerve regeneration. Thirty Sprague‐Dawley rats underwent left sciatic nerve transection and repair according to three experimental groups: epineurial coaptation (EC), EC with BDNF delivered by an osmotic pump (EC‐BDNF), and EC with BDNF and CNTF delivered similarly (EC‐BDNF/CNTF). Nerve regeneration was assessed using sciatic functional indices, quantitative histomorphology, and molecular analysis for proteins associated with nerve regeneration. Analysis of variance (ANOVA) comparing all groups at each time point demonstrated significant differences between groups on days 20, 30, 40, 50, 60, and 80. A paired, two‐tailed Students t‐test with the Bonferroni correction for multiple comparisons demonstrated that at 40 days postoperatively, animals in the EC‐BDNF/CNTF group (n = 7) manifested superior functional recovery compared with those in the EC group (n = 9) and those in the EC‐BDNF group (n = 9) (P < 0.001 and P < 0.05, respectively). At 80 days, the animals in both the EC‐BDNF (P < 0.01) and EC‐BDNF/CNTF (P < 0.05) groups demonstrated greater functional recovery compared with those in the EC group, with no significant difference between the two factor groups at the endpoint. Morphometric analysis demonstrated that nerves from animals in the EC‐BDNF/CNTF group had the largest mean axon diameters as compared with those from the EC (proximal: P < 0.001, distal: P < 0.05) and EC‐BDNF(proximal: P < 0.01) groups. No significant differences were seen in nerve cross‐sectional area. In distal nerve segments, Western blot analysis revealed that expression of myelin‐associated glycoprotein was higher than control for the EC group and lower than control for both the EC‐BDNF and EC‐BDNF/CNTF groups. We conclude that BDNF/CNTF combined treatment increases the early rate of functional sciatic nerve regeneration over treatment with BDNF alone, although the degree of maximal recovery was similar at the conclusion of the experiment.

Dilatational versus Standard Tracheostomy: A Meta-Analysis

The advent of percutaneous dilatational tracheostomy (PDT) was initially viewed by otolaryngologists with great skepticism. The purpose of this study was to compare the complications of PDT with those of standard tracheostomy (ST) by a meta-analysis of randomized studies. We found that ST had a fivefold higher rate of complications than did PDT, and these complications were often more severe. We conclude that PDT is a safer procedure for elective tracheostomy in carefully selected patients, ie, those with normal-sized necks.

Metastatic renal cell carcinoma to the nose

A 74-year-old man was evaluated for a large fungating, friable mass protruding from his left nasal vestibule causing intermittent epistaxis and nasal obstruction (Fig 1). In 1993 he had been diagnosed with renal cell adenocarcinoma, which had been treated with a radical left nephrectomy. In 1997 mediastinal and right lung masses developed and were seen on chest roentgenograms. Biopsy specimens demonstrated these to be metastatic renal cell carcinoma (RCC). One year later, the nasal mass developed. Biopsy specimens of this friable nasal mass revealed metastatic RCC. Palliative resection of this lesion was performed for management of his epistaxis and partial left nasal obstruction. RCC is the most common malignant renal tumor and typically affects men between the ages of 30 and 60 years.1 RCC has a higher incidence in men than in women and can metastasize to any location in the body. The most common metastatic sites are the lungs (75%), regional lymph nodes (65%), and bones and liver (40%); the incidence in the head and neck is approximately 15%.2 After lung and breast carcinoma, RCC is the third most common infraclavicular tumor to metastasize to the head and neck.2 Metastasis to the nose is extremely rare, and to our knowledge there have been only 25 reported cases in the literature.1-4 When the paranasal sinuses are included, RCC is the most common primary malignancy to cause metastases to this location.2 Swelling, nasal obstruction, and pain can all be nonspecific symptoms, but epistaxis is the chief symptom in more than 70% of cases.2 Histopathology reveals poorly defined cells with abundant clear cytoplasm and indistinct cytoplasmic borders (Fig 2). Epistaxis is caused by the richly surrounding vascular stroma. With electron microscopy, it has been elucidated that the epithelium of the proximal renal tubular cell is the origin of RCC.3 The highly unpredictable ability of RCC to metastasize anywhere has experts theorizing on the routes of spread. The most favored theory at this point is emboli from RCC spreading to the head and neck via Batson’s paraspinal venous plexus. This is a rich venous anastomosis with the prevertebral, vertebral, and epidural systems. A tumor embolus could travel from the kidney to the inferior vena cava in anterograde fashion. An increase in intraabdominal and intrathoracic pressure could push the embolus in retrograde fashion through the anastomotic venous system into the head and neck.3 It also has been postulated that an embolus could travel via a hematogenous or lymphatic route. The 5-year survival rate after a nephrectomy is approximately 60% to 75%.3 In those patients who have a solitary metastasis, the treatment is radical excision and nephrectomy, with an approximate 5-year survival of 35%.2 The prognosis of patients with multiple metastases is poor, and the 5-year survival is 0% to 7%.3 Most patients with RCC die of complications of their tumor or as a direct result of distant metastases.3

Functional recovery following nerve injury and repair by silicon tubulization: Comparison of laminin-fibronectin, dialyzed plasma, collagen gel, and phosphate buffered solution

PURPOSE This study was designed to investigate the potential for enhancement of peripheral nerve regeneration by the manipulation of the neural microenvironment with laminin-fibronectin solution (LF), dialyzed plasma (DP), collagen gel (CG), or phosphate buffered saline (PBS) in a silicon tubulization repair model. METHOD A rat sciatic nerve model of injury and repair was used to study the effects of exogenous matrix precursors (contained in LF or DP), CG or PBS on nerve regeneration. A total of 50 Sprague-Dawley rats underwent left sciatic nerve transection and repair by silicon tubulization. The silicon tubules were either left empty (E), or filled with solutions of LF, DP, CG, or PBS. Nerve function was assessed preoperatively and then postoperatively, every 10 days for 90 days using sciatic functional indexes (SFI). On postoperative day 90, the sciatic nerves were harvested for histologic analysis and the posterior compartment muscles of each animal were harvested and weighed. Molecular analysis for two proteins associated with neural regeneration was performed on the nerve segments. RESULTS All five animal groups demonstrated equivalent functional recovery. Comparison of the rate of recovery and mean maximal recovery between each group revealed no statistically significant differences, with P-values ranging from 0.30 to 0.95. Posterior compartment muscle masses were similar in all groups except for LF, whose animals had muscle masses 8-9% lower than CG, PBS, or E (P < 0.05). CONCLUSION Alteration of the regenerating neural microenvironment with exogenous matrix precursors (LF, DP), CG or PBS failed to improve sciatic functional recovery after nerve transection and silicon tubulization in this model. From this study, we conclude that LF, DP, CG, and PBS do not enhance the rate or degree of recovery of peripheral nerve function across a narrow gap when nerves are repaired by silicon tubulization.

Functional recovery of transected nerves treated with systemic BDNF and CNTF.

The purpose of this study was to investigate the effect of systemic co‐injections of ciliary neurotrophic factor (CNTF) and brain‐derived neurotrophic factor (BDNF) on the functional recovery of transected sciatic nerves repaired by epineurial coaptation (EC) or collagen tubulization (CT). Forty Sprague‐Dawley rats underwent transection of their sciatic nerves and repair by either EC or CT. With each repair technique, systemic injections of neurotrophic factors or control injections of lactated Ringers solution were given. This resulted in four treatment groups: EC, EC + BDNF/CNTF, CT, and CT + BDNF/CNTF. Nerve function was assessed using sciatic functional indices (SFI). Animals whose nerves were repaired by CT (P = 0.01), CT + BDNF/CNTF (P = 0.04), and EC + BDNF/CNTF (P = 0.04) all had better functional recovery than those whose nerves were repaired by EC. There were no significant differences among these three groups, however. Animals in the CT group manifested the most rapid rate of recovery (P = 0.02 compared with EC). Collagen tubulization and systemic co‐injections of BDNF/CNTF improve the rate and extent of sciatic functional recovery after nerve repair. The improvement in recovery conferred is not additive.

Factors Related to Outcome of Salvage Therapy for Isolated Cervical Recurrence of Squamous Cell Carcinoma in the Previously Treated Neck: A Multi-Institutional Study

OBJECTIVE: The goal was to identify factors associated with the outcome of salvage therapy for patients with isolated cervical recurrences of squamous cell carcinoma in the previously treated neck (ICR-PTN). STUDY DESIGN AND SETTINGS: A tumor registry search for ICR-PTN patients was performed at 7 participating institutions, and the charts were reviewed. Kaplan-Meier plots for survival and time until rerecurrence were used to evaluate the significance of associated variables. RESULTS: Median survival and time until re-recurrence were both 11 months. Survival was better in patients with the following characteristics: nonsurgical initial neck treatment, negative initial disease resection margins, no history of prior recurrence, ipsilateral location of the ICR-PTN relative to the primary, and use of surgical salvage. CONCLUSIONS: By pooling the experience of 7 US tertiary care medical centers, we have identified 5 factors that are associated with outcome of salvage therapy for ICR-PTN. SIGNIFICANCE: Consideration of these factors, as well as the reviewed literature, should facilitate patient selection for salvage protocols. (Otolaryngol Head Neck Surg 2000; 123:368-76.)

Effect of blended CO2 and erbium:YAG laser irradiation on normal and keloid fibroblasts: a serum-free study.

OBJECTIVE The purpose of this study was to determine the effect of combined CO2 and Er:YAG laser irradiation on normal (NF) and keloid (KF) facial dermal fibroblast production of TGF-beta1 and bFGF. BACKGROUND DATA Keloids produce excess collagen. TGF-beta1 is integral to the growth and stimulation of fibroblasts and collagen; bFGF inhibits collagen synthesis. TGF-beta1 and bFGF production influence wound healing and may be manipulated by laser irradiation. MATERIALS AND METHODS Human normal fibroblasts (NF) and keloid fibroblasts (KF) (2 x 10(4) cells/mL in serum-free media) were exposed to 1.7 J/pulse Er:YAG laser energy and CO2 delivered at either 3 or 5 W and at a duty cycle of 25%, 50%, or 100%. TGF-beta1 and bFGF were assayed using a quantitative ELISA. RESULTS KF demonstrated a statistically significant mean population doubling time (PDT) when compared with NF (p=0.01). Irradiated KF and NF had longer PDTs than controls. All NF, excluding one irradiated group, and the three KF treated with 3 W secreted more bFGF than controls. Irradiated KF secreted less TGF-beta1 than controls. Significance was reached with the two groups exposed to 3 W at a duty cycle of 25% and 50% (p=0.04 and 0.05, respectively). All irradiated NF secreted less TGF-beta1 than controls. CONCLUSION The combined CO2 and Er:YAG laser increased the release of bFGF, which has been shown to promote tightly organized collagen bundles, and decreased the concentration of TGF-beta1, which has also been shown to promote fibrosis formation. This laser may have a future role in keloid treatment, as well as normal facial scar prevention.