Influence of vertebral column distraction on spinal cord volume: an experimental study in a goat model.

INTRODUCTION: Spinal cord injury may be related to excessive distraction of the spinal cord during surgical correction of spinal deformities by vertebral column resection. This study aimed to investigate how vertebral column distraction influences spinal cord volume to establish the safe range in a goat model. MATERIALS AND METHODS: A vertebral column resection was performed on the tenth thoracic vertebra of 11 goats. The spinal cord was distracted until the somatosensory evoked potential signals were decreased to 50 % from baseline amplitude or were delayed by 10 % of the baseline peak latency. The osteotomy segment was stabilized with a PEEK mesh cage filled with bone graft, and the pedicle screws on the rods were then tightened in this position. Spinal cord volume was calculated using Mimics software, and T10 height, disk height, osteotomy segment height, and spinal segment height were measured using the MRI image workstation. RESULTS: Three goats were excluded, and data obtained from the eight remaining goats were analyzed. The safe limit of distraction distance was 11.8 ± 3.65 mm, and the distraction distance was strongly correlated with the difference between the pre- and postoperative measurements (d value) of spinal cord volume per 1 mm of osteotomy segment height (r = -0.952, p < 0.001), but was not correlated with T10 body height (r = 0.16, p = 0.71), spinal segment height (r = 0.29, p = 0.49), disk height (r = -0.12, p = 0.98), or the d value (pre-post) of spinal cord volume per 1 mm of spinal segment height (r = 0.45, p = 0.26). The mean d value (pre-post) of spinal cord volume per 1 mm of osteotomy segment height was 10.05 ± 0.02 mm(3) (range 10.02-10.08 mm(3)). CONCLUSION: The maximum change in spinal cord volume per 1-mm change in height was in the osteotomy segment, and its safe limit was 10.05 ± 0.02 mm(3). The safe limit of spinal cord distraction can be calculated using the spinal cord volume per unit 1-mm change in height.

Relationship between Spinal Cord Volume and Spinal Cord Injury due to Spinal Shortening.

Vertebral column resection is associated with a risk of spinal cord injury. In the present study, using a goat model, we aimed to investigate the relationship between changes in spinal cord volume and spinal cord injury due to spinal shortening, and to quantify the spinal cord volume per 1-mm height in order to clarify a safe limit for shortening. Vertebral column resection was performed at T10 in 10 goats. The spinal cord was shortened until the somatosensory-evoked potential was decreased by 50% from the baseline amplitude or delayed by 10% relative to the baseline peak latency. A wake-up test was performed, and the goats were observed for two days postoperatively. Magnetic resonance imaging was used to measure the spinal cord volume, T10 height, disc height, osteotomy segment height, and spinal segment height pre- and postoperatively. Two of the 10 goats were excluded, and hence, only data from eight goats were analyzed. The somatosensory-evoked potential of these eight goats demonstrated meaningful changes. With regard to neurologic function, five and three goats were classified as Tarlov grades 5 and 4 at two days postoperatively. The mean shortening distance was 23.6 ± 1.51 mm, which correlated with the d-value (post-pre) of the spinal cord volume per 1-mm height of the osteotomy segment (r = 0.95, p < 0.001) and with the height of the T10 body (r = 0.79, p = 0.02). The mean d-value (post-pre) of the spinal cord volume per 1-mm height of the osteotomy segment was 142.87 ± 0.59 mm3 (range, 142.19-143.67 mm3). The limit for shortening was approximately 106% of the vertebral height. The mean volumes of the osteotomy and spinal segments did not significantly change after surgery (t = 0.310, p = 0.765 and t = 1.241, p = 0.255, respectively). Thus, our results indicate that the safe limit for shortening can be calculated using the change in spinal cord volume per 1-mm height.

Outcomes and xerostomia after postoperative radiotherapy for oral and oropharyngeal carcinoma.

BACKGROUND: We compared outcomes and xerostomia grade after postoperative intensity-modulated radiation therapy (IMRT) and conventional radiotherapy (RT) in patients with oral and oropharyngeal carcinoma. METHODS: Eighty-eight patients with oral cavity (n = 77) and oropharyngeal (n = 11) carcinoma underwent postoperative IMRT (n = 44) or conventional RT (n = 44). Outcomes, failure patterns, volume, doses, salivary gland V30, and xerostomia grade were evaluated. The median follow-up was 53 months (range, 48-58 months). The median interval from surgery to RT was 4 weeks (range, 3-6 weeks). RESULTS: Twenty-one patients (7 and 14 for the IMRT and conventional RT groups, respectively) experienced local-regional failure. For the IMRT group, all 7 local-regional failures occurred in the high-dose target volumes. For the conventional RT group, there were 12 in-field failures, 1 at the margin, and 1 out-of-field. Nine patients experienced distant failure (5 and 4 for the IMRT and conventional RT groups, respectively). The 4-year local-regional control, disease-free survival (DFS), overall survival (OS), and distant-metastasis rates for the IMRT and conventional RT groups were 84.1% versus 68.2% (p = .055), 68.2% versus 52.3% (p = .091), 70.5% versus 56.8% (p = .124), and 11.4% versus 9.1% (p = .927), respectively. Xerostomia grade after RT was lower for IMRT compared to conventional RT (p < .001). CONCLUSION: Postoperative IMRT for oral and oropharyngeal carcinoma significantly improves mean dose, salivary gland V30, and xerostomia grade when compared to conventional RT. The predominant failure pattern was local. No differences were found in survival outcomes between both groups. There was a marginal difference in local-regional control.

Protecting the oral mucosa in patients with oral tongue squamous cell carcinoma treated postoperatively with intensity-modulated radiotherapy: a randomized study.

OBJECTIVES/HYPOTHESIS: Is the severity of acute oral mucositis in patients who receive postoperative intensity-modulated radiotherapy (PO-IMRT) for oral tongue squamous cell carcinoma (SCC) reduced by sparing the oral mucosa outside of the planning target volume (PTV)? STUDY DESIGN: Prospective, randomized trial. METHODS: Forty-eight patients with oral tongue SCC who received PO-IMRT at our institution were randomized to two groups: the oral-sparing (OR-SP) group and oral-unsparing (OR-USP) group. For the OR-SP group (n = 24), the oral mucosa outside of the PTV was spared. Furthermore, the mucosa including the bilateral cheeks, upper lip, and lower lip was defined as the united site and given <32 Gy. For the OR-USP group (n = 24), none of the oral mucosa was protected. The severity of clinical acute mucositis in each patient was assessed weekly during PO-IMRT until completely healed. Oral mucositis was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0. Dosimetry and therapeutic measures related to acute mucositis between the two groups were compared. RESULTS: During PO-IMRT, no patient experienced grade 4+ acute mucositis in any oral site. Compared to the OR-USP group, there was less grade 2 and 3 mucositis in the united site of the OR-SP group (0% and 25% vs. 45.8% and 54.2%, respectively; P = .000). Also, the mean dose to the united site was significantly lower with OR-SP compared to OR-USP (41.8 ± 7.4 Gy vs. 58.8 ± 2.2 Gy; P = .000). The OR-SP group was associated with significant reductions in the use of analgesics (P = .043) and intravenous antibiotics (P = .039). No recurrences were detected in the vicinity of the spared oral mucosa (the united site) during a median follow-up time of 30 months. CONCLUSIONS: OR-SP PO-IMRT for patients with oral tongue SCC resulted in a significant decrease in the severity of acute mucositis and improved quality of life. The sparing of the oral mucosa outside of the PTV is safe and does not compromise oncologic outcomes.

Impact of salivary gland dosimetry on post-IMRT recovery of saliva output and xerostomia grade for head-and-neck cancer patients treated with or without contralateral submandibular gland sparing: a longitudinal study.

PURPOSE: To observe the recovery of saliva output and effect on xerostomia grade after intensity-modulated radiotherapy (IMRT) with or without contralateral submandibular gland (cSMG) sparing and to assess the impact of salivary gland dosimetry on this recovery among patients with head-and-neck cancer. METHODS AND MATERIALS: Between May 2007 and May 2008, 52 patients with head-and-neck cancer received definitive (n=5 patients) and postoperative (n=47 patients) IMRT at our institution, with at least one parotid gland spared. Of these patients, 26 patients with a low risk of recurrence in the cSMG region underwent IMRT and had their cSMGs spared (cSMG-sparing group). The remaining 26 high-risk patients had no cSMGs spared (cSMG-unspared group). Xerostomia grades and salivary flow rates were monitored at five time points (before IMRT and at 2, 6, 12, and 18 months after IMRT). RESULTS: Average mean doses and mean volumes receiving 30 Gy (V30) of the cSMGs were lower in the cSMG-sparing group than in the cSMG-unspared group (mean dose, 20.4 Gy vs. 57.4 Gy; mean V30, 14.7% vs. 99.8%, respectively). Xerostomia grades at 2 and 6 months post-IMRT were also significantly lower among patients in the cSMG-sparing group than in the cSMG-unspared group, but differences were not significant at 12 and 18 months after IMRT. Patients in the cSMG-sparing group had significantly better mean unstimulated salivary flow rates at each time point post- IMRT as well as better mean stimulated salivary flow rates at 2 months post-IMRT. CONCLUSIONS: Recovery of saliva output and grade of xerostomia post-IMRT in patients whose cSMGs were spared were much better than in patients whose cSMGs were not spared. The influence of the mean doses to the cSMG and parotid gland on the recovery of saliva output was equivalent to that of the mean V30 to the glands.

[The effect of MAB225 on radiosensitivity of salivary gland adenoid cystic carcinoma].

PURPOSE: To observe the effect of epidermal growth factor receptor's monoclonal antibody(MAB225) on radiosensitivity of salivary gland adenoid cystic carcinoma cell. METHODS: Bi-fluorescence stain ,MTT test and fluorescence flow cytometry(FCM) were used to observe the apoptosis rate and radiosensitizing effect for MAB225 on ACC-2 cell.SPSS11.0 software package was used for data analysis. RESULTS: Through bi-fluorescence stain, MTT test and fluorescence flow cytometry(FCM),it was found that MAB225 combined with radiation treatment produced a 3-fold induction of apoptosis rate, whereas exposure to radiation alone induced apoptosis only 1 fold, compared to the control group. CONCLUSION: MAB225 enhanced radiosensitivity and decreased survival rates of ACC-2 cell in vitro after radiation.

Radiation-induced volume changes in parotid and submandibular glands in patients with head and neck cancer receiving postoperative radiotherapy: a longitudinal study.

OBJECTIVES/HYPOTHESIS: To investigate changes in parotid and submandibular gland volumes of patients with head and neck cancer treated with postoperative intensity-modulated radiotherapy (IMRT) or conventional radiotherapy (CRT), and to relate the volume changes to different mean radiation therapy (RT) doses to the parotid and submandibular glands. METHODS: Between May 2007 and May 2008, 82 head and neck cancer patients (oral cavity cancer, 71; oropharynx cancer, 11) were treated with surgery and postoperative RT (IMRT, 40; CRT, 42) at our institution. Every patient underwent four computed tomography (CT) scans: one before RT, one after 3 weeks or at the 15th fraction of RT, one upon completing RT, and one at 2 months after RT; 39 of 82 patients had an additional CT scan at 6 months after RT. A dose-volume histogram was used to evaluate the mean volumes of patients' parotid and submandibular glands and mean RT doses to the glands on every CT scan. Altogether, 241 salivary glands (parotid, 162; submandibular, 79) were analyzed. The volume changes of the glands were evaluated against three levels of mean gland doses: <30 Gy, 30 to 50 Gy, and >50 Gy. RESULTS: The mean RT doses to spared parotid glands, spared submandibular glands, and irradiated submandibular glands in patients treated with IMRT were 22.21 Gy, 18.26 Gy, and 52.19 Gy, respectively. The mean doses to parotid and submandibular glands in patients treated with CRT were 50.22 Gy and 62.09 Gy, respectively. The average volume loss rates in parotid glands after 3 weeks of RT, at the end of RT, and 2 months after RT versus before RT were 20.01%, 26.93%, and 27.21%, respectively. The average volume loss rates in submandibular glands after 3 weeks of RT, at the end of RT, and 2 months after RT versus before RT was 11.49%, 16.76%, and 16.29%, respectively. Parotid and submandibular glands did not continue to shrink after completing RT. We observed more volume loss during RT in the parotid glands than in the submandibular glands. The average rates of volume loss during the first 3 weeks of RT (20.01% and 11.49%, respectively) were larger than in the last 3 weeks of RT (8.57% and 6.0%, respectively). No significant differences were observed in the mean volumes of both parotid and submandibular glands between the end of RT, 2 months post-RT, and 6 months post-RT (P > .05). Volume loss at higher doses (>30 Gy) to the glands was significantly larger than at low doses (<30 Gy; P < .001). CONCLUSIONS: The parotid and submandibular glands shrunk during RT, but the parotid glands shrunk more than the submandibular glands. These gland volume reductions correlated significantly with the mean dose to the irradiated glands; the spared glands showed few changes.

The influence of intraarterial high-dose cisplatin with concomitant irradiation on arterial microanastomosis: an experimental study.

OBJECTIVE: In this experimental study with rabbits, the influence of intraarterial high-dose cisplatin with concomitant irradiation on arterial microanastomoses was evaluated to determine their impact on free-tissue transfers. METHODS: The right and left iliac arteries of 10 rabbits were injected with 150 mg/m of cisplatin (group 1). To serve as physiological controls, the iliac arteries of 10 other rabbits were injected with the same volume of saline (group 2). Hypofractionated radiotherapy was given to the right inguinal area of all rabbits using a Co unit, 1.25 MeV, and an SSD of 80 cm for 25 Gy at 5 fractions a day for 5 days (groups 1A and 2A) and the left inguinal areas remained unirradiated (groups 1B and 2B). Both femoral arteries of all 20 rabbits were transected and anastomosed using microsurgical techniques on day 7 after the treatment. All femoral artery anastomoses were examined under anesthesia for pulsatile blood flow 14 days after the surgery. Arteries, including the anastomotic site, were harvested and fixed for histologic evaluation by light microscopy and transmission electron microscopy. RESULTS: Microscopic evaluation showed that all femoral artery anastomoses had good, pulsatile blood flow. Histologic examination of the femoral artery anastomotic site revealed changes of the arterial walls that varied between the groups. Evidence of intimal changes included detachment of endothelial cells in the intimal layer, edema of the endothelial cells in the intima, intimal thickening, separation of the intima from the tunica media, and collagen deposition. Evidence of damage to the tunica media included vacuolation and disarray of the smooth muscle cells, fibrinoid necrosis, and hemorrhage. The damage was most pronounced in the arteries that received both intraarterial cisplatin and radiotherapy (group 1A). The degree of damage diminished in the arteries of the radiotherapy-alone group (group 2A) and the intraarterial cisplatin-alone arteries (group 1B) compared with the control arteries (group 2B). Despite the arterial damage after irradiation and/or cisplatin, the patency rates after vascular anastomosis were 100% for every group. CONCLUSIONS: Although damage to the arterial walls in the group that received intraarterial high-dose cisplatin with concomitant irradiation was most obvious, there were no differences in the patency rates after vascular anastomosis between any of the groups. Thus, after intraarterial high-dose cisplatin with concomitant irradiation, the femoral arteries can be used with caution as recipient vessels for free-tissue transfer.

[Effects of intra-arterial perfusion of cisplatin combined with concomitant radiation therapy on the healing of microvascular anastomoses: an experimental study in rabbits].

PURPOSE: To investigate the effects of intra-arterial perfusion of cisplatin and concomitant radiation therapy on the microvascular structure and the healing of anastomoses. METHODS: Three different treatments including intra-arterial perfusion of saline, intra-arterial perfusion of cisplatin, intra-arterial perfusion of saline and 25 Gy radiation therapy as well as intra-arterial perfusion of cisplatin and 25 Gy radiation therapy were conducted in 40 femoral arteries of 20 rabbits, which divided into 4 groups, control group, intra-arterial chemotherapy group, radiation therapy group and combined treatment group accordingly. The bilateral femoral arteries were transected and anastomosed using microsurgical technique on 7th day after the treatments were completed. The effects of different treatments on the microvascular structure and the patency rates of anastomoses were investigated. RESULTS: The evidences of chronic damage to the vascular wall were observed in 4 groups. The changes in the combined treatment group were most serious. The damage to arterial wall in the radiation therapy group, chemotherapy group, and control group decrease gradually in order. Although the damages of the vascular wall were observed, there were no differences in the patency rates after microvascular anastomoses. CONCLUSION: These vessels can be used with caution as recipient vessels for free tissue transfer.

[Inhibiting effect of EGFR monoclonal antibody on proliferation of oral squamous cell carcinoma].

OBJECTIVE: To investigate the inhibiting effect of epidermal growth factor receptor (EGFRmAb) on proliferation of oral squamous cell carcinoma (SCC). METHODS: Tca8113 squamous cell carcinoma cell line was treated with different concentration of EGFRmAb. Cell growth curve, clone inhibition rate, cell cycle redistribution and the expression of p27kip1 were analyzed. RESULTS: EGFRmAb inhibited proliferation of oral SCC, leaded to elevation of cell proportion of G1phase cell, decreased the proportion of S phase cell and upregulated the express of p27kip1. CONCLUSION: EGFRmAb inhibited the proliferation of oral SCC, which related with G1 phase arrest of tumor cell.