B. Han

Central Malignant Salivary Gland Tumors of the Jaw: Retrospective Clinical Analysis of 22 Cases

PURPOSE As a review of central malignant salivary gland tumor cases in Southwest China in the past 20 years, this study provided the clinical, radiologic, and pathologic information of these rare lesions. PATIENTS AND METHODS In our study, 22 cases of central malignant salivary gland tumor treated between 1986 to 2006 at West China Stomatology Hospital of Sichuan University were retrospectively analyzed. A thorough review of clinical records was carried out and the histologic diagnosis was revised using the 2005 WHO criteria. RESULTS The average age of patients was 46.5 years old, and the peak incidence age of the tumors was in the fourth, fifth, and sixth decades. The male:female ratio was 0.47:1. The clinical manifestation included swelling of the jaw, pain, paraesthesia, tooth mobility, and pain. All the lesions were radiolucent regions with an ill-defined margin. The most frequent histologic type was the mucoepidermoid carcinoma. Local extensive resection of the primary focus was the primary treatment. CONCLUSION Central malignant salivary gland tumors often occurred in the middle-aged patients, and there were more cases in the mandible than in the maxilla. The diagnosis should be based on the case history, clinical, pathologic, and radiologic examinations. The major treatment was extensive resection of primary focus.

Preventing post-surgical complications by modification of parotidectomy

UNLABELLED The aim of this paper was to evaluate the complications of patients with benign parotid disease treated by modified parotidectomy through conserving the sub-superficial musculoaponeurotic system (sub-SMAS), great auricular nerve (GAN), and reconstruction by sternocleidomastoid flap (SF). Between 1997 and 2001, 226 patients with benign parotid disease were operated. Patients were retrospectively assigned to four groups according to the surgical technique: I (94) sub-SMAS flap, II (42) sub-SMAS and reconstruction by SF, III (57) subcutaneous flap (sub-CF), and IV (33) sub-CF and reconstruction by SF. The GAN was conserved in all patients. RESULTS After a minimum follow up of 24 months, Freys syndrome (FS) and cosmetic appearance were evaluated. The incidence of FS in Groups I and II was significantly lower than in patients with sub-CF. A significant difference between the groups with and without SF existed in preventing the concavity of the auricular lobule at 3, 6 and 12 months after operation, but no significant difference existed between Group I vs II and Group II vs III at 12 months after surgery. The sensitivity of the auricular lobule was not changed. CONCLUSIONS Complete parotidectomy with sub-SMAS successfully prevents FS, and combined with SF provides improved aesthetic results. Conserving GAN can prevent the sensation of the auricular lobule.

Selective intra-arterial infusion of rAd-p53 with chemotherapy for advanced oral cancer: a randomized clinical trial

BackgroundIn this study, a combination of recombinant adenoviral p53 (rAd-p53) gene therapy and intra-arterial delivery of chemotherapeutic agents for treatment of oral squamous cell carcinoma was evaluated.MethodsIn total, 99 patients with stage III or IV oral carcinoma who had refused or were ineligible for surgery were enrolled in a randomized, placebo-controlled, double-blind, phase III clinical trial. They were randomly assigned to group I (n = 35; intra-arterial infusion of rAd-p53 plus chemotherapy), group II (n = 33; intra-arterial infusion of rAd-p53 plus placebo chemotherapy), or group III (n = 31; intra-arterial infusion of placebo rAd-p53 plus chemotherapy).ResultsThe median length of follow-up was 36 months (range, 3 to 86 months). During follow-up, 16 patients in group I, 20 in group II, and 22 in group III died. Group I (48.5%) had a higher complete response rate than groups II (16.7%) and III (17.2%) (P = 0.006). The rate of non-responders in group I was significantly lower than that in groups II and III (P < 0.020). A log-rank test for survival rate indicated that group I had a significantly higher survival rate than group III (P = 0.019). The survival rate of patients with stage III but not stage IV oral cancer was significantly higher in group I than in group III (P = 0.015, P = 0.200, respectively). The survival rate of patients with stage IV did not differ significantly among the three groups. Or the 99 patients, 63 patients experienced adverse events of either transient flu-like symptoms or bone marrow suppression, while 13 patients had both these conditions together. No replication-deficient virus was detected in patient serum, urine, or sputum. rAd-p53 treatment increased Bax expression in the primary tumor of 80% of patients, as shown by immunohistochemical staining.ConclusionsIntra-arterial infusion of combined rAd-p53 and chemotherapy significantly increased the survival rate of patients with stage III but not stage IV oral cancer, compared with intra-arterial chemotherapy. Intra-arterial infusion of combined rAd-p53 and chemotherapy may represent a promising alternative treatment for oral squamous cell carcinoma.Trial registrationChiCTR-TRC-09000392 (Date of registration: 2009-05-18).

Predicting extracapsular spread of head and neck cancers using different imaging techniques: a systematic review and meta-analysis.

This study compared the diagnostic ability of computed tomography (CT), magnetic resonance imaging (MRI), ultrasonography (US), and positron emission tomography/CT (PET/CT) for extracapsular spread. MEDLINE, EMBASE, China National Knowledge Infrastructure, Chinese Biomedical Literature Database, and Sciencepaper Online databases were searched. The mean sensitivity of CT was 0.77, specificity was 0.85, positive likelihood ratio (LR+) was 4.839, negative likelihood ratio (LR-) was 0.287, diagnostic odds ratio (DOR) was 19.239, area under the summary receiver operating characteristic curve (AUC) was 0.8615, and Q* was 0.7922. The mean sensitivity of MRI was 0.85, specificity was 0.84, LR+ was 4.615, LR- was 0.191, DOR was 60.270, AUC was 0.9454, and Q* was 0.8844. The sensitivity and specificity of PET/CT were both 0.86. The mean sensitivity of US was 0.87 and specificity was 0.75. Overall, CT had the lowest sensitivity (P=0.0355); specificity was similar for all methods (P=0.1159). CT and MRI had equivalent summary diagnostic efficacy (AUC and Q*) (P>0.05). This evidence indicates that CT might have a relatively lower sensitivity when diagnosing ECS, and that CT and MRI may be similarly effective in diagnosing ECS. MRI showed positive trends in diagnosing ECS. Evidence was lacking for PET/CT and US diagnosis. More related studies are required to confirm these inconclusive results.

Expression of p53, p21(CIP1/WAF1) and eIF4E in the adjacent tissues of oral squamous cell carcinoma: establishing the molecular boundary and a cancer progression model.

The present study evaluated the expression of key molecules and the status of DNA in both oral squamous cell carcinoma (OSCC) and adjacent tissues to establish a molecular surgical boundary and provide a cancer progression model. Biopsy samples from 50 OSCC patients were divided into T (cancer), P1 (0–0.5 cm), P2 (0.5–1 cm), P3 (1–1.5 cm) and P4 (1.5–2 cm) groups based on the distances from the visible boundary of the primary focus. Twenty samples of normal mucosa were used as controls. We used immunohistochemical staining and flow cytometry to evaluate p53, p21CIP1/WAF1, eIF4E and Ki-67 expression and to determine DNA status, respectively. Sub-mucosal invasion was present in the P1 and P2 groups as determined by haematoxylin and eosin staining. Mutant p53 expression decreased gradually from cancerous to normal mucosae, whereas p21CIP1/WAF1 expression displayed an opposite trend. eIF4E expression decreased from cancerous to normal mucosae. Ki-67 expression, the heteroploidy ratio, S-phase fraction and proliferative index decreased gradually with the distance from the tumour centre. Based on these results, we suggest that the resection boundary in OSCC surgery should be beyond 2 cm from the tumour. Additionally, the adjacent tissues of the primary focus could be used as a model for assessing cancer progression.International Journal of Oral Science (2015) 6, doi:10.1038/ijos.2015.5; published online 27 March 2015

Prognostic and proliferative evaluation of ameloblastoma based on radiographic boundary

Ameloblastoma is a benign odontogenic tumor with an aggressive biological behavior, and the surgical treatment frequently results in failure for the postoperative recurrence. The aim of this article was to investigate whether the proliferative ability and prognosis of ameloblastoma could be evaluated by the radiographic boundary. The ameloblastoma cases treated by the conservative therapy in our hospital between 1981 and 2001 were divided into three groups based on the nature of the radiographic borders of the lesions. The biologic behavior was evaluated by Ki-67 antibody immunohistochemically. Comparisons of prognosis and Ki-67 expression were carried out by statistic methods. There were 24 cases of well-defined edge with sclerosis (group I), 41 cases of well-defined edge without sclerosis (group II) and 32 cases of ill-defined edge (group III). The recurrent rates were 29.2% in group I, 43.9% in group II and 62.5% in group III (P<0.05). The cells in group III expressed the highest Ki-67 level (P<0.05). The radiographic boundary could be used as one of indicators in evaluating the proliferative ability of ameloblastoma and the patients prognosis, which was consistent with Ki-67 expression.

Clinical evaluation on controlling postoperative recurrence of oral squamous cell carcinoma by intracavity brachytherapy

The purpose of this research was to evaluate the clinical outcome and factors influencing postoperative intracavity brachytherapy in treating oral squamous cell carcinoma. As a part of their primary treatment, 108 patients received postoperative intracavity brachytherapy only and 85 patients received postoperative intracavity brachytherapy with external radiotherapy. 78 patients were given surgical treatment alone as a control. The survival rates and local tumor control rates were calculated and the therapeutic effects of various treatment methods compared. Overall 5- and 10-year survival rates for patients receiving surgical treatment alone, postoperative intracavity brachytherapy with or without external radiotherapy were 59% and 17%, 73% and 47%, 78% and 57%, respectively. The corresponding local tumor control rates were 53% and 51%, 73% and 71%, 75% and 73%, respectively. Surgical treatment with postoperative intracavity brachytherapy controlled tumor recurrence effectively (p<0.01) and improved survival rates (p<0.01). UICC stages, grading and tumor site had an important influence on overall survival and local tumor control rates. Local tumor excision followed by postoperative intracavity brachytherapy achieved good local tumor control and survival rate, and may be considered as a new and routine treatment for oral cancer.

Factors to Consider When Deciding on the Type of Free-Flap Reconstruction of Head and Neck Soft Tissue Defects

Objectives: The aim of the study was to evaluate the functional and aesthetic outcomes on donor and recipient sites and to determine the effects of technical factors including flap thickness and vessel diameters measured by ultrasonography as well as the size of the defect and postoperative volume reduction of the flaps measured by magnetic resonance imaging (MRI). Methods: In patients who had undergone soft tissue reconstructive surgery between March 2013 and March 2016 using 55 anterolateral thigh flaps (ALTFs), 30 radial forearm flaps (RFFs), and 18 latissimus dorsi flaps (LDFs), color Doppler ultrasonography was performed to measure the thickness of the flap at the site of the perforator. Preoperative color Doppler ultrasound examinations of the blood vessel diameters of donor and recipient sites were carried out. Results: 97.1% of flaps showed complete survival and 2.9% complete failure (2 ALTFs and 1 LDF). The difference in flap volume of ALTFs, RFFs, and LDFs between MRI 1 (3-6 weeks) and MRI 2 (6-18 months) was 27.6, 17.9, and 36.1%, respectively. Conclusion: Proper selection of the flap is important for the optimization of the aesthetic and functional outcomes. Ultrasound, the surgeons experience and the extension and nature of the defect play a key role in the selection of the flap.

Abstract 1232: Regulation of ARHI and p53 gene on the programmed cell death of oral cancer cells

Proceedings: AACR 106th Annual Meeting 2015; April 18-22, 2015; Philadelphia, PA Background: Oral cancer is one of the most common diseases which severely threaten human health. As a “gate-keeper” gene, p53 plays a significant role in promoting apoptosis of cancer cells. Meanwhile, it has been showed that ARHI (aplasia ras homologue member I) gene could regulate the autophagy of cancer cells to promote the programmed cell death. The present study was aimed to research the regulation of ARHI and p53 gene on the programmed cell death of oral cancer cells. Study Design: Firstly, the expression of ARHI gene was tested in the normal tissues and oral cancer cells. Then, we transfected wild-type p53 and ARHI gene by the recombinant adenovirus into the oral cancer cell line (Cal-27) and evaluated the levels of apoptosis by cell morphology, flow cytometry and TUNEL assay. After that, the evaluations of autophagic levels were carried out by the transmission electron microscope, and by the expression of LC3B via immunofluorescence and western-blot. The functions of P53 and ARHI gene were evaluated by the key factors in PI3K-Akt pathway and the downstream proteins. Finally, we testified the results of cellular researches by a xenograft mouse model. Results: The expressions of ARHI gene were lower in oral cancer cells than that in normal tissues. The mRNA and protein expressions of p53 and ARHI increased substantially in Cal-27 cells after gene transfections, and the expressions of bcl-2,bax, p21, stat3 were changed accordingly, which verified the activation of the two genes function. It was noteworthy that the expression of p53 gene could rise by the ARHI gene transfection while the expression of ARHI could not, which showed that ARHI could be the upstream factor of p53. It was found that the programmed cell death was promoted in Cal-27 cells 48 hours after the gene transfections, which was shown as the cytoplasmic condensation and nuclear shrinkage. In the same time, the proliferation rates of Cal-27 cells decreased, and apoptosis increased significantly. The autophagic progresses were increased initially, but were blocked in the following steps. The phosphorylation of Akt in sites of Thr308 and Ser473 were decreased after gene transfections. The phosphorylation of 4E-BP1 was decreased to enhance the binding rate between 4E-BP1 and eIF4E, and expressions of the downstream functional factors, such as c-myc, cyclin D1, bcl-2, FGF, VEGF, EGFR, were decreased. The tumor growth curves were decreased tremendously after intra-tumoral injection of p53 and ARHI recombinant adenovirus in the animal models, which were consistent with cellular studies. Conclusion: P53 and ARHI could inhibit the phosphorylation of key factors in PI3K-Akt pathway, thus restraining the expressions of functional factors to promote programmed cell death in oral cancer. Citation Format: Yi Li, Shan-Wei Shi, Chun-Jie Li, Bo Han, Long-Jiang Li. Regulation of ARHI and p53 gene on the programmed cell death of oral cancer cells. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1232. doi:10.1158/1538-7445.AM2015-1232

A retrospective study on the complications after the modified parotidectomy in the benign tumors of parotid gland

OBJECTIVE A retrospective clinic study is presented of surgical patients undergoing a modified parotidectomy with conserving the sub-superficial musculoaponeurotic system (sub-SMAS) and great auricular nerve and reconstructing by the stemocleidomastoid flap (SF). The incidence of clinical complications was observed after the parotidectomy. METHODS 226 patients were divided randomly into four groups. Group 1 (94 cases) were operated by the conserving the sub-SMAS. Group 2 were operated by the sub-SMAS and constructed by SF. Group 3 (57 cases) were treated by the subcutaneous flap (sub-CF). Group 4 (33 cases) were received by sub-CF and SF. The surgical technique was described and the incidence of clinical Freys syndrome was evaluated by minor test (starch-iodine test) and observed gustatory sweating syndrome. The feeling and concave of the region of auricular lobule were followed up. RESULTS The incidence of Freys syndrome in group 1 (5.32%) or group 2 (4.76%) was significantly lower than that of group 3 (49.1%) or group 4 (51.5%) through by subjective observation and minor test (P < 0.005). The significance between group with SF and group without SF existed in protecting the concave of the region of auricular lobule (P < 0.05). The feeling of the region of auricular lobule had no change by preserving the great auricular nerve. CONCLUSION There was good effect to prevent gustatory sweating syndrome in parotidectomy of reserve parotid fascia. The aesthetics and sense of the region of auricular lobule could be prevented by using SF and reserving the great auricular nerve.