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Biomedical subjects

J G Spector

Publications and source records attributed to J G Spector.

At least 19 recordsLinked to original sources

Delayed regional metastases, distant metastases, and second primary malignancies in squamous cell carcinomas of the larynx and hypopharynx.

OBJECTIVE: To determine the impact of delayed regional metastases, distant metastases, and second primary tumors on the therapeutic outcomes in squamous cell carcinomas of the larynx and hypopharynx. STUDY DESIGN: Chart review and statistical analysis. METHODS: A retrospective tumor registry analysis was made of patients with squamous cell carcinomas of the larynx and hypopharynx who were treated with curative intent in the Department of Otolaryngology-Head and Neck Surgery and the Radiation Oncology Center of the Washington University School of Medicine (St. Louis, MO) between January 1971 and December 1991 and developed delayed regional metastases (2 y after treatment), distant metastases, and second primary malignancies. RESULTS: In 2550 patients, the mean age (59.8 y), sex (8.5 male patients and 1 female patient), and tumor differentiation did not affect the incidence of delayed distant, regional, or second primary malignancies. The overall incidence of delayed regional metastases was 12.4% (317/2550 patients); distant metastases, 8.5% (217/2550); and second primary tumors, 8.9% (228/2550), with a 5-year disease-specific survival of 41%, 6.4%, and 35%, respectively. Second primary malignancies were not statistically related to the origin of the primary tumor, tumor staging, or delayed regional and distant metastases (P =.98). Delayed regional metastases and distant metastases were related to advanced primary disease (T4 stage), lymph node metastases (node positive [N+]), tumor location (hypopharynx), and locoregional tumor recurrence (P < or =.028). Advanced regional metastases at initial diagnosis (N2 and N3 disease) increased the incidence of delayed and distant metastases threefold (P =.017). These two metastatic parameters were significantly greater in hypopharyngeal tumors than in laryngeal tumors (P =.037). The incidences of delayed regional metastases by anatomical location of the primary tumor were as follows: glottic, 4.4%; supraglottic, 16%; subglottic, 11.5%; aryepiglottic fold, 21.9%; pyriform sinus, 31.1%; and posterior hypopharyngeal wall, 18.5%. The incidences of distant metastases were as follows: glottic, 4%; supraglottic, 3.7%; subglottic, 14%; aryepiglottic fold, 16%; pyriform fossa, 17.2%; and posterior hypopharyngeal wall, 17.6%. Seventeen hypopharyngeal tumors (2%) presented with M1 disease. Delayed regional metastases to the ipsilateral treated neck had a significantly worse survival prognosis than delayed metastases to the contralateral nontreated neck (P =.001). CONCLUSIONS: Conclusions are as follows: 1) The incidence of second primary tumors is independent from the primary tumor staging and distant and delayed regional metastases. The highest incidence occurred in patient groups with the highest disease-free survival rates (P =.0378). 2) Highest incidence of delayed and distant metastases occurred in hypopharyngeal tumors and was three times greater than in laryngeal cancers (P =.028). 3) Salvage therapeutic rates were poor for delayed metastases to the ipsilateral treated nodes and distant metastases as compared with contralateral neck metastases and second primary tumors (P =.001). 4) Delayed and distant lymph node metastases were significantly higher in advanced primary disease (T4 stage), locoregional recurrences, and regional disease (N2 and N3) (P =.028) in both the larynx and hypopharynx. 5) The higher incidence of delayed and distant metastatic disease was related to more advanced initial tumor presentation in hypopharyngeal cancer as compared with laryngeal cancer (P =.039). 6) Incidence of distant metastases was greatest between 1.5 and 6 years after initial treatment with a mean incidence being less than or equal to 3.2 years.

Adult↗

Rabbit facial nerve regeneration in autologous nerve grafts after antecedent injury.

OBJECTIVE: The effect of incomplete antecedent injuries on subsequent facial nerve regeneration within cable graft repairs is not known. The purpose of this study is to compare facial nerve regeneration after an immediate and delayed neural cable graft repair. METHOD: Rabbit facial nerve regeneration after complete transectional injuries of the buccal division was compared in two experimental models. In one, a 10-mm segment of the nerve was transected, rotated 180 degrees, and immediately repaired as a cable graft (N=8). In the second, a preliminary nerve crush was allowed to recover over a 4-week period and a 10-mm segment of nerve centered on the crush site was then transected, rotated 180 degrees, and delay repaired as a cable graft (N = 7). Data are presented as total numbers of regenerating myelinated axons that traverse the surgical repair to innervate the cable graft and distal nerve stumps, as well as the percentage of regenerating neurites compared with preoperative pooled and individual controls. Subpopulations of regenerating neurons are delineated to quantify the pattern of neural innervation. RESULTS: Five weeks after cable graft repair both groups had similar myelinated outgrowth from the proximal nerve stump across the proximal anastomosis to innervate the cable graft (3995 +/- 1209 vs. 3284 +/- 651; P = .89). However, the delayed repair group had more intrafascicular regeneration within cable grafts (2261 +/- 931 vs. 1660 +/- 1169; P = .02) and distal nerve stump (1532 +/- 281 vs. 445 +/- 120; P = .004) than the immediate repair group. The immediate repair group had greater extrafascicular nerve regeneration in the cable graft (2335 +/- 1954 vs. 437 +/- 236; P = .001) and more myelin and axonal debris in pre-existing neural fascicles of the cable graft (P = .02) and distal nerve stump (463 +/- 187 vs. 103 +/- 87; P = .02). CONCLUSIONS: Antecedent priming lesions do not enhance axonal survival as determined by regenerating myelinated axonal counts. However, antecedent injuries enhance the efficiency of neural innervation of the affected mimetic musculature by increasing the number of myelinated intrafascicular neural regenerants in the cable graft and distal nerve stump. This is accomplished by two factors: increased perineural fibrosis and decreased intrafascicular myelin and axonal debris.

Animals↗

Management of stage II (T2N0M0) glottic carcinoma by radiotherapy and conservation surgery.

BACKGROUND: The best therapeutic approach for the treatment of stage II (T2N0M0) glottic carcinoma is controversial. METHODS: A retrospective tumor registry data retrieval of patients with stage II glottic carcinoma treated with curative intent at Washington University Medical Center-Barnes Hospital between January 1971 and December 1989 (surgery) and December 1995 (radiotherapy) was performed. RESULTS: Among 134 patients with stage II glottic carcinomas treated with curative intent and function preservation, there were 47 patients treated with low dose radiotherapy (median dose, 58.5 Gy at 1.5-1.8 Gy daily fractions), 16 patients with high dose radiotherapy (67.5-70 Gy) at higher daily fractionation doses (2-2.25 Gy), and 71 patients underwent conservation surgery. The overall local control rate was 85%. The overall salvage rate was 68%. The 5-year actuarial and disease specific survivals were 81.5% and 92%, respectively. Unaided phonation was achieved in 84.4% of the patients. An incidence of 10.4% regional metastases, 2.2% distant metastases, and 6% second primary tumors was documented. There were no statistical differences in local control, voice preservation, and 5-year actuarial and disease specific cure rates between conservation surgery and high dose radiation (p = .89). Low dose radiation had statistically lower local controls, 5-year survival, and voice preservation (p = .014). In advanced T2B disease, treating the ipsilateral neck nodes reduced regional metastases (p = .02). CONCLUSIONS: High dose and daily fractionation (70 Gy at 2 Gy daily fraction doses) radiation achieved results equivalent to those of conservation surgery in 5-year local control, survival, and voice preservation. In advanced T2B disease, treatment of the ipsilateral neck nodes by radiotherapy or functional neck dissection reduced regional metastases.

Adult↗

Stage I (T1 N0 M0) squamous cell carcinoma of the laryngeal glottis: therapeutic results and voice preservation.

BACKGROUND: The therapeutic outcomes for voice preservation in Stage I (T1 N0 M0) glottic carcinoma, treated with conservation surgery, radiation therapy, and endoscopic resection, are controversial. METHODS: A retrospective tumor registry retrieval of data on patients treated with curative intent at Washington University Medical Center-Barnes Hospital between January 1971 and December 1990 for the surgical group, January 1971 to December 1985 for the low-dose radiation group, and January 1986 to January 1995 for the high-dose radiation group, was performed. RESULTS: The 659 patients with Stage I (T1 N0 M0) glottic carcinoma treated with curative intent were subdivided into four groups: (1) 90 patients received low-dose radiation (mean dose 58 Gy, range 55-65 Gy, daily fractionation 1.5-1.8 Gy); (2) 104 patients received high-dose radiation (mean dose 66.5 Gy, range 65-70 Gy, daily fractionation 2-2.25 Gy); (3) 404 patients underwent conservation surgery; and (4) 61 patients had endoscopic resection. T1A (85%) and T1B (15%) disease was equally distributed among the groups. The anterior commissure was involved in 38 patients in the radiation therapy groups and 56 patients in the surgical groups. The overall local control was 89%. The overall local salvage was 84%. The overall unaided laryngeal voice preservation was 90%. The overall 5-year disease specific and actuarial survival rates were 95% and 81%, respectively. Prevalence of 2% regional metastases, 1.2% distant metastases, and 14% second primary malignancies were documented. The cure rate was 69% for regional metastases, 13% for distant metastases, and 44% for second primary malignancies. There were 5 complication deaths (0.1%), and 38 (6%) patients died of intercurrent disease. The use and dose of tobacco products was significantly increased in patients who died of intercurrent disease (p = 0.004) or developed second primary malignancies (p = 0.024). No significant difference was observed among the four therapeutic groups in the 5-year cause-specific survival rate (p, 0.68). Actuarial survival was significantly decreased in the low-dose radiation therapy group as compared with the other three therapeutic groups (p = 0.04). Initial local control was poorer for the endoscopic (77%) and low-dose radiation (78%) groups as compared with the high-dose radiation (89%) and conservation surgery (92%) groups (p = 0.02) but significant differences were not found for ultimate local control following salvage treatment. Unaided laryngeal voice preservation was similar for high-dose radiation (89%), conservation surgery (93%) and endoscopic resection (90%), but significantly poorer for low-dose radiation (80%; p = 0.02). T1B disease (N = 94) had similar local control and voice preservation with conservation surgery (87%) and high-dose radiation (88%) but lower results with low-dose radiation and endoscopic resections (67% unaided laryngeal voice preservation; p = 0.02). CONCLUSION: (1)The four therapeutic groups achieved similar rates of disease specific survival and ultimate local control. (2) Low-dose radiation was associated with significantly lower overall actuarial survival and unaided laryngeal voice preservation. (3) Endoscopic resection was associated with a significantly lower initial local control rate, but following salvage therapy achieved equivalent results to the other treatment methods. (4) Patients with (T1 N0 M0) glottic carcinoma had similar survival, local control, and unaided laryngeal voice preservation rates with high-dose radiation, conservation surgery, and endoscopic resections, but not with low-dose radiation therapy. (c) 1999 John Wiley & Sons, Inc. Head Neck 21: 707-717, 1999.

Adult↗

Effects of thrombin and protease nexin-1 on peripheral nerve regeneration.

Thrombin and serine protease inhibitors such as protease nexin-1 (PN-1) have been implicated in neurite outgrowth activity. We compared rat sciatic nerve regeneration in 10-mm silicone tubes, bridging an 8-mm nerve gap, that were prefilled with thrombin (1.5 IU) and PN-1 (50 micrograms/mL or 1 mg/mL) to those filled with saline solution (control). Neural regeneration and fibrinoid matrix progression (deposition of extracellular matrix) were analyzed at 1, 4, 17, and 21 days after silicone tube implantation. At 1 and 4 days after implantation, thrombin reduced fibrinoid matrix length propagation from both the proximal and distal transected nerve stumps, but PN-1 and saline did not interfere with matrix progression (p < .05). Seventeen days after implantation, the number of silicone tubes containing myelinated neuronal regenerates at the mid-tube region was 1 of 6 for thrombin, 6 of 9 for PN-1, and 6 of 10 for saline solution. Twenty-one days after implantation, 11 of 11 tubes with saline solution, 9 of 11 with PN-1 at 1 mg/mL, and 7 of 9 with PN-1 at 50 micrograms/mL had myelinated neural regenerates in the mid-silicone tube region, while only 2 of 9 thrombin-containing silicone tubes contained myelinated axons. There was no statistically significant difference in myelinated neurite regenerates at 17 and 21 days after implantation among silicone tubes prefilled with saline solution and PN-1 (50 micrograms/mL or 1 mg/mL). Thrombin interfered with matrix progression and significantly reduced the number of myelinated neurite regenerates (p = .01). The PN-1 and saline solutions did not inhibit matrix progression or affect the number of myelinated axonal regenerates (p = .92).

Amyloid beta-Protein Precursor↗

Axonal regeneration in severed peripheral facial nerve of the rabbit: relation of the number of axonal regenerates to behavioral and evoked muscle activity.

The minimum number of regenerating facial nerve myelinated motor axons that are required to innervate and activate the mimetic musculature is not known. We compare rabbit facial nerve regeneration following complete transectional injuries of the buccal division to the evoked and behavioral muscle activities of the quadratus labii superioris muscle of the rabbit in three experimental models: end-to-end direct anastomosis (N = 4), 8-mm autologous nerve grafts (N = 8), and 10-mm silicone chamber implants (N = 40). Data are presented as total numbers of regenerating myelinated axons that traverse the surgical repair and innervate the fascicles of the transected distal nerve stump, as well as the percentage of regenerating neurites, as compared to the preoperative normal controls. Five weeks after neural repair, direct end-to-end anastomosis regained more myelinated axons across the reconstructed defect (2,632 +/- 1,232; 67%) than silicone tube implants (2,006 +/- 445; 51%) or autologous cable graft repairs (1,660 +/- 1,169; 42%). However, only a small percentage of myelinated fibers innervated the intrafascicular region of the distal transected neural stump in direct anastomosis (948 +/- 168; 24%), silicone tube implants (670 +/- 275; 17%), or autologous nerve grafts (445 +/- 120; 12%) in rabbits that regained evoked and behavioral mimetic muscle activity. All rabbits with direct anastomosis and neural cable grafts regained motor activity, despite the fact that 66% of regenerating motor neurites in cable graft repairs and 54% in direct anastomosis were collateral sprouts that did not contribute to effective muscle activity. In 17 rabbits with neural regenerates within the silicone tube implants that did not regain mimetic activity, the mean number of regenerating myelinated motor axons across the defect was 504 +/- 419 (13%), and the mean number of axons that innervated the distal transected nerve stump fascicles was 277 +/- 128 (7%). Therefore, the minimal number of motor axons that is required to activate the quadratus labii superioris muscle is 12% of the original motor axon population of the normal buccal nerve division.

Anastomosis, Surgical↗

Neural repair in facial paralysis: clinical and experimental studies.

Acute facial nerve injuries involving the total facial nerve (n = 202) and its segmental branches (n = 63) were repaired with a variety of neural (n = 225) and myofascial transfer (n = 40). A system for evaluating results based on facial symmetry and tone at rest, recovery of voluntary mimetic activity, synkinesis, and recovery of selective function in discrete facial nerve divisions is presented. The best results were achieved with immediate direct end-to-end neural-epineural anastomotic repairs. The least favorable results were seen with myofascial transpositions and long extratemporal rerouted autologous nerve grafts. A series of tissue culture and animal experiments were used to examine structural changes in neural repair. The requirements for successful motoneuron regeneration, causes of synkinesis and methods for nerve stump coaptation are elucidated. Tubulation experiments demonstrated the need for neurotrophic and neuropromotive factors. Problems associated with the use of autologous nerve grafts are discussed.

Anastomosis, Surgical↗

Comparison of rabbit facial nerve regeneration in nerve growth factor-containing silicone tubes to that in autologous neural grafts.

Previous reports suggest that nerve growth factor (NGF) enhanced nerve regeneration in rabbit facial nerves. We compared rabbit facial nerve regeneration in 10-mm silicone tubes prefilled with NGF or cytochrome C (Cyt C), bridging an 8-mm nerve gap, to regeneration of 8-mm autologous nerve grafts. Three weeks following implantation, NGF-treated regenerates exhibited a more mature fascicular organization and more extensive neovascularization than Cyt C-treated controls. Morphometric analysis at the middle of the tube of 3- and 5-week regenerates revealed no significant difference in the mean number of myelinated or unmyelinated axons between NGF- and Cyt C-treated implants. However, when the numbers of myelinated fibers in 5-week regenerates were compared to those in their respective preoperative controls, NGF-treated regenerates had recovered a significantly greater percentage of myelinated axons than Cyt C-treated implants (46% versus 18%, respectively). The number of regenerating myelinated axons in the autologous nerve grafts at 5 weeks was significantly greater than the number of myelinated axons in the silicone tubes. However, in the nerve grafts the majority of the axons were found in the extrafascicular connective tissue (66%). The majority of these myelinated fibers did not find their way into the distal nerve stump. Thus, although the number of regenerating myelinated axons within the nerve grafts is greater than that of axons within silicone tube implants, functional recovery of autologous nerve graft repairs may not be superior to that of intubational repairs.

Animals↗

Squamous cell carcinoma of the pyriform sinus: a nonrandomized comparison of therapeutic modalities and long-term results.

From January 1964 through December 1991, 408 patients with squamous cell carcinomas involving the pyriform sinus were treated at Washington University Medical Center. Their ages ranged from 29 to 83 years (mean, 62.3; median 59) and the male to female ratio was 5:1. The mean duration of symptoms prior to diagnosis was 3.9 months (range 1 to 32 months) and 89% had a smoking or ethanol history. Sixty-seven percent had T3 or T4 lesions and 87% were stage III or IV at presentation. Sixty-nine percent had neck metastases. The treatment strategy varied with respect to radiation and reconstruction. Prior to 1978, preoperative radiation (3.5 to 5000 cGy) was used. Postoperative radiation was given thereafter (600+ Gy). Since 1982, flap reconstruction (usually pectoralis major myocutaneous) has been used to close the partial laryngopharyngectomy (PLP) defect. Almost all N0 necks were treated by radiation or surgery and all N1-N3 lesions were treated by combined therapy. Pyriform tumors were subdivided into three groups: 1. one-wall lesions (n = 48), 2. medial-wall lesions which involved the aryepiglottic fold or supraglottis (N = 267), and 3. two- or three-wall lesions which extended to the pyriform apex or post-cricoid region (N = 93). Ninety-five patients had single-modality therapy and 302 had combined treatment. Two hundred seven patients had conservation surgery (PLP) and 157 had total laryngopharyngectomy alone or in combination with radiation. Thirty-three patients were treated by radiation alone. Eleven patients were excluded from the study because of distant metastases (TxNxM1) at presentation. The cumulative survival (NED) at 5, 10, 15, and 20 years was 56%, 35%, 31%, and 20%, respectively. The cumulative locoregional control rate was 71%. At 5 years (NED), the cure rates for one-wall lesions (73%) were better than for medial-wall lesions (63%) or 2- and 3-wall lesions (49%). One-wall lesions were smaller, medial-wall lesions behaved similar to supraglottic tumors, and two- or three-wall tumors behaved as hypopharyngeal tumors. The cure rates were related to T stage with T1 + T2 > T3 + T4 (28%). Neck metastases reduced the cure rate by 26% and N1 > N2-N3 by an additional 12%. Other factors contributing to therapeutic failure were distant metastases (17.7%), second primary tumors (6.2%; oropharynx and lung were most common), and intercurrent disease fatalities (9.5%). The secondary therapeutic salvage rate was 44% for surgery and 32% for radiation therapy. The therapeutic complication rate was 19% with 3.6% leading to fatality.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

Squamous cell carcinomas of the aryepiglottic fold: therapeutic results and long-term follow-up.

Three hundred fifteen patients with squamous cell carcinomas involving the aryepiglottic (A-E) folds were treated between January 1964 and December 1991. The age ranged from 39 to 87 years (mean, 62.4 years; median, 61.3 years) and the male-to-female ratio was 5:1 (54 women and 261 men). Symptom duration prior to diagnosis was 4.8 months. Eighty percent of patients had T3 and T4 lesions and 56.3% had neck metastases at presentation. Six patients (1.8%) had distant metastases and were excluded from this study. Clinically the tumors presented as either exophytic infiltrating lesions which were confined to the A-E fold (n = 57) or mucosally spreading tumors which extended to the lateral supraglottis or pyriform sinus (n = 258). Prior to 1978 preoperative radiation (3000 to 5000 cGy) was used. Higher doses of postoperative radiation (5000 to 6000+ cGy) were used thereafter. After 1982 the use of myocutaneous flaps for closure of partial laryngopharyngectomy defects was routine. Almost all N0 neck disease was treated by radiation or surgery. Combined therapy was used in N1-N3 disease. One quarter of the patients had single-modality therapy (25.7%; 81 patients) with a cumulative 5-year disease-free survival of 53%. The remainder of the patients (n = 234) had combined therapy with a cumulative 5-year survival of 67.2%. The latter group had 163 conservation surgeries and 121 total laryngectomy resections. The 5-year disease-free survival for preoperative radiation with surgery (68%) and postoperative radiation with surgery (64%) was similar. Those treated by radiation alone had a 34% 5-year disease-free survival and those treated with surgery alone had a 61% 5-year disease-free survival. The cumulative locoregional control rate was 77%. The cumulative disease-free survival at 5, 10, 15, and 20 years is 66%, 57%, 55%, and 55%, respectively. Infiltrating tumors had a better disease-free survival (by more than 10%) than spreading tumors. The 5-year survival rates were separated well by clinical stages of tumors. In patients with T1 tumors the 5-year survival was 87%; in those with T2 tumors, 80%; in those with T3 tumors, 78%; and in those with T4 tumors, 41%. The survival rate was greater in those with N0 tumors than in those with N+ tumors by 25% and greater in those with N1 tumors than in those with N2 + N3 tumors by an additional 18%. The overall complication rate was 26% and in 7.7% these were fatal.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

Rabbit facial nerve regeneration in NGF-containing silastic tubes.

Previous reports suggest that exogenous nerve growth factor (NGF) enhanced nerve regeneration in rabbit facial nerves. Rabbit facial nerve regeneration in 10-mm Silastic tubes prefilled with NGF was compared to cytochrome C (Cyt. C), bridging an 8-mm nerve gap. Three weeks following implantation, NGF-treated regenerates exhibited a more mature fascicular organization and more extensive neovascularization than cytochrome-C-treated controls. Morphometric analysis at the midtube of 3- and 5-week regenerates revealed no significant difference in the mean number of myelinated or unmyelinated axons between NGF- and cytochrome-C-treated implants. However, when the number of myelinated fibers in 5-week regenerates were compared to their respective preoperative controls, NGF-treated regenerates had recovered a significantly greater percentage of myelinated axons than cytochrome-C--treated implants (46% vs. 18%, respectively). In addition, NGF-containing chambers reinnervated a higher percentage of myelinated axons in the distal transected neural stumps (49% vs. 34%). Behavioral and electrophysiologic studies demonstrated spontaneous and induced activities in the target muscles when approximately one third of the myelinated axons were recovered in the midchamber (1280 axons). Horseradish peroxidase (HRP) studies demonstrated retrograde axonal transport to the midchamber and proximal transected neural stump. PC12 bioassay demonstrated persistent NGF activity in the intrachamber fluids at 3 (5:1 dilution) and 5 (2:1 dilution) weeks of entubation. Electrophysiologic tests demonstrated a slow conduction velocity of a propagated electrical impulse (43.5 m/s-1 vs. 67 m/s-1) and shallow wide compound action potential. In wider defects (15-mm chambers) and longer entubation periods (7 weeks), no regeneration or NGF activity was seen. Therefore, exogenous NGF provides an early but limited neurotrophic effect on the regeneration of the rabbit buccal division of the facial nerve and a limited behavioral and physiological improvement in the target muscles.

Animals↗

Ossification patterns of the tympanic facial canal in the human fetus and neonate.

Dehiscences in the bony facial canal are comparatively common in the human adult. The highest incidence occurs in the tympanic segment of the facial nerve near the region of the oval window. Thirty-three fetal temporal bones, ranging from 16 to 40 weeks' gestation, and four from 1, 2, 4 and 12 weeks' postpartum neonates, were studied to evaluate the normal patterns of ossification of the fallopian canal of the tympanic facial nerve segment in the human. The tympanic facial nerve segment elongates three-fold during this period (from 1 mm to 3 mm). The ossification starts at 21 weeks' gestation anteriorly from apical otic ossification centers and at 26 weeks from canalicular ossification centers near the stapedius muscle. The ossification proceeds in an anterior-to-posterior direction as two periosteal shelves of bone surround the facial nerve. The superior periosteal bony ledge contributes 75% of the circumference of the fallopian canal. The anterior ossification center forms over 83% of the fallopian canal length. The two centers fuse post partum near the region of the oval window. The anatomic location of the facial nerve, nerve branching, and neural vasculature precede ossification. In 80% of the paired temporal bones, this ossification pattern appears to be symmetrical. The patterns and incidence of bony dehiscences within the tympanic fallopian canal segment can be explained by these observations. This study demonstrates that fallopian canal dehiscences are not congenital anomalies, but variations of normal developmental anatomic processes.

Cartilage↗

Facial nerve regeneration through semipermeable chambers in the rabbit.

Peripheral neural regeneration, over a 10-mm transectional gap, was determined in 70 rabbit buccal divisions of the facial nerve using two entubational systems (semipermeable and impermeable silicone chambers) prefilled with three natural occurring media (serum, blood, and saline) during a 5-week period. The number of myelinated axonal regenerates at the midchamber and at 2 mm in the distal transected neural stump were counted in each group and compared to pooled myelinated axonal counts in 9 normal rabbit buccal divisions of the facial nerve. Semipermeable porous chambers had an overall greater regeneration success rate (75% vs. 42.8%) and regained, on the average, a higher number of myelinated axons (51.4% vs. 26.1%) than silicone chamber regenerates. Semipermeable chambers prefilled with serum or blood had significantly higher regeneration success rates, myelinated axonal counts, and percentages of neural innervation of the distal transected neural stump. Both entubational systems produced similar axonal counts with intraluminal saline. The highest overall success rate (93.7%) and average number of myelinated axons per chamber (3072) were achieved in semipermeable chambers prefilled with serum. The greatest variability in myelinated axonal counts (0 to 3266 axons) and percentage of distal stump innervation (5.5% to 98.1%) was seen in silicone chambers filled with saline. The percentage of myelinated axons from the midchamber that innervated the distal stump was greater in semipermeable chambers with blood (73%) and serum (54%) than in silicone saline chambers (43%). On the average, the distal stumps from semipermeable chambers filled with serum (47%) and blood (33.5%) regained a higher percentage of normal myelinated axonal counts than silicone-saline chambers (12.5%). These results suggest that both the construction of entubational chamber and the intraluminal medium can have significant influence on neurite regeneration. Semipermeable chambers prefilled with serum have a strong neurite-promoting potential in peripheral neural regeneration of rabbit facial nerves.

Analysis of Variance↗

Management of temporal bone carcinomas: a therapeutic analysis of two groups of patients and long-term followup.

Fifty-one patients with squamous cell carcinomas arising within the temporal bone were subdivided into two groups. The initial group of 17 patients, seen between 1960 and 1980, were reviewed retrospectively and staged into four subgroups on the basis of initial tumor presentation and location (i.e., external auditory canal, superficial invasion, deep invasion, and tumors beyond the temporal bone). After treatment in a variety of surgical and radiotherapeutic combinations, the 5-year cure rates were: 70%, 70%, 50%, and 9%, respectively. Thirty-four patients, seen between 1980 and 1989, were placed in a new prospective protocol for combined surgery and postoperative irradiation. These patients were subdivided into the same subgroups on the basis of tumor location. The surgical procedures were formalized to be more encompassing (i.e., external canal tumors were treated by sleeve resection of the internal auditory canal and tympanic membrane, superficial invasion by superficial temporal bone resection, deep tumors by radical temporal bone resection, and those beyond the temporal bone by an infratemporal fossa approach). Radical neck dissections were performed where needed. The irradiation dosage was increased to 6250+ cGy, with a 4:1 ratio in favor of electrons for deeper penetration, and the fields were widened. At 36.6-month average followup, the cure rates were: 100%, 100%, 70%, and 65%, respectively. Six of ten patients with neck metastases at presentation had tumor recurrence or distant disease (60%).

Adult↗

Facial nerve regeneration through autologous nerve grafts: a clinical and experimental study.

Human facial nerve regeneration was compared in two systems: autologous neural cable grafts (N = 56) and direct end-to-end anastomosis (N = 34). The data were analyzed based on the following criteria: facial symmetry and muscle tone at rest, degree of total facial reinnervation, voluntary motion, synkinesis, and electrophysiologic testing. Facial tone and symmetry at rest, and electrophysiologic tests were similar, while voluntary motion and facial reinnervation were decreased and synkinesis increased in the autologous cable graft repairs. Electrophysiologic tests failed to distinguish between the two repair methods in successful regenerates. Neural cable grafts were associated with more mass movement and less fine precise emotive facial movement. Excellent cable graft repair results diminish with time because of continual progressive synkinesis, which may take up to 4 years to develop. Eight-millimeter neural cable graft repairs of the buccal division of the facial nerve in rabbits (N = 8) demonstrate, at 5 weeks, equal myelinated and more unmyelinated axons than in the normal nerve controls. Neural cable graft repairs demonstrate two features not found in the normal nerve: 1. myelin debris and 2. two subpopulations of axons--extrafascicular and intrafascicular. Myelin debris predisposes towards extrafascicular axon regeneration. Extrafascicular axons are the major neurite regenerates (63%). Intrafascicular axons are the major reinnervators of the distal transected nerve stump. Electrophysiologic studies demonstrate decreased conduction velocities which are related to the number and size of myelinated axonal regenerates. The implications for neurite reinnervation of the autologous cable graft and their role in synkinesis are discussed.

Action Potentials↗

Supraglottic carcinoma: impact of radiation therapy on outcome of patients with positive margins and extracapsular nodal disease.

Seventy-nine patients with supraglottic carcinoma treated between 1966 and 1985 are reviewed. All patients were treated with surgery and postoperative radiation therapy. Thirty-five percent of the patients had positive margins at the site of resection of the primary tumor. Of the 25 patients who had positive nodal disease, 13 patients (52%) had either extracapsular extension or soft-tissue or adjacent organ invasion, referred to in composite as "grave signs." The median follow-up of the patients was 4.9 years and all patients were followed for a minimum of 3 years. The disease-free survival for all patients was 76% at 2 years and 71% at 3 years. The locoregional control rate for all patients was 70%. This study demonstrates that there is no difference in local recurrence or disease-free survival, or time to recurrence relative to the status of the surgical margins, which may be a benefit of the postoperative radiation therapy. This study also demonstrates that there is an increase in the number of patients with grave signs with increasing nodal stage. The rate of neck recurrence in patients with grave signs was substantially higher (54%) than in patients without grave signs (8%), even though these patients also had positive lymph nodes. Interestingly, there was also a higher rate of local recurrence among patients who had grave signs. Patients receiving doses higher than 6000 cGy to the primary site had fewer local failures, although within each group of patients with positive or negative surgical margins the differences in survival were minimal.

Adult↗

Early stages of facial nerve regeneration through silicone chambers in the rabbit.

The early stages of rabbit peripheral facial nerve regeneration [N = 16], over a 10-mm transectional gap, were analyzed at 1, 3, and 5 weeks of buccal nerve entubation in silicone chambers prefilled with saline. Normal nerve pooled data were obtained in nine nerves. Chronologic morphologic and morphometic light and electron microscopic computer-captured data reveal that the regeneration process can be subdivided into four stages: 1. The establishment of an acellular intergap matrix; 2. the ingrowth of mesodermally derived cells (macrophages, fibroblasts, endothelial cells, etc.) to form an intergap scaffolding; 3. the ingrowth of ectodermally derived cells (neurons, Schwann's cells, etc.) to reconstitute the transected peripheral nerve; and 4. neural maturation by progressive axonal enlargement, myelination, and compartmentalization. The first two stages occur during the first week, the third stage during the third week, and the fourth stage from the fifth week onwards of neural entubation. Morphometic analyses indicate that total neuroregenerates increase in number from 303 +/- 286 to 2693 +/- 1334 (+/- values are standard deviations) and myelination of axons increases from 12% to 48% during the third to fifth week of entubation. The thickness of the myelin (g-ratio) increases from 0.89 +/- .01 to 0.74 +/- .06 (SD) during the same period of time. At the end of the fifth week of entubation, the midchambers contain, on the average, 1279 +/- 980 myelinated axons (30% of normal counts) and 483 (+/- 11.2%) axons cross the chambers to innervate the distal transected neural stump (12.5%). Specific target-organ (quadratus labii superioris muscle) activity can be recaptured with a smaller number (12.5%) of regenerating myelinated axons from the buccal division of the facial nerve during the fifth week of entubation.

Animals↗