Prognostic Model and Nomogram for Early-Onset Adenoid Cystic Carcinoma of Head and Neck: A Retrospective SEER-Based Analysis.

BACKGROUND: Adenoid cystic carcinoma of head and neck (ACCHN) is an uncommon head and neck cancers, whose predilection age is 40 to 60. Some studies have revealed that early-onset cancers, such as colorectal cancers and esophageal adenocarcinoma, might present some unique clinicopathological features and have different prognosis with late-onset ones. However, little is known about the early-onset ACCHN. This study aimed to develop a prognostic nomogram for overall survival (OS) of patients younger than 40 with ACCHN. METHODS: Cases with ACCHN from 1975 to 2016 were retrieved from SEER-18 program. Demographic, clinical, and survival outcomes data of patients were identified for further analysis. The caret package was used to randomly divide early-onset patients into a training cohort and a validation cohort. A prognostic nomogram was constructed based on the univariate and multivariate Cox analysis. The discriminative ability and calibration power of the nomogram was evaluated by the concordance index (C-index), calibration curve, and receiver operating characteristic (ROC) curve. RESULTS: A total of 5858 cases with ACCHN were selectively retrieved from SEER program in this study. The number of patients younger than 40, which was defined as early-onset ACCHN in this study, was 825. Based on the outcomes of multivariate analysis, tumor size, chemotherapy, surgery, and stage were selected for the construction of nomogram to predict 10-year OS. The C-index was 0.792 (95%CI 0.760-0.823) and 0.776 (95%CI 0.720-0.832) in the training and validation set, respectively. The area under the ROC curve values were 0.875 (95%CI 0.810-0.940) and 0.833(95%CI 0.754-0.912). The calibration plot indicated that this nomogram had proper calibration in both the training and validation cohorts. CONCLUSION: A novel prognostic nomogram for early-onset ACCHN was constructed and validated in this study. This nomogram could be applied for assisting clinicians to more accurately assess the prognosis of young patients, which might facilitate clinical decision-making and subsequent follow-up.

Advancements in MAPK signaling pathways and MAPK-targeted therapies for ameloblastoma: A review.

Numerous signal transduction pathways are closely associated with the occurrence, development, and prognosis of ameloblastoma (AM). Mitogen-activated protein kinase (MAPK) is a serine/threonine-specific protein kinase that transduces intracellular signals in critical cellular phenomena. A number of recent analyses have reported that the MAPK signaling pathway contributes significantly to AM. High-throughput DNA sequencing methods, such as next-generation sequencing using Illumina have yielded advancements in studies on MAPK signaling pathways and their association with AM; in particular, BRAF V600E is mediated by the activation of the Ras/Raf/MAPK pathway. This review discusses advancements in studies on MAPK signaling pathways and MAPK-targeted inhibitors or antibodies, along with the merits and demerits of MAPK-targeted therapies, finally followed by a discussion regarding more efficient potential MAPK-targeted therapies to treat AM with few side effects, thereby providing novel insights into targeted therapy for AM.

[Expression and clinical significance of p53 and autophagy-related gene Beclin1 in salivary pleomorphic adenoma and carcinoma in pleomorphic adenoma].

PURPOSE: To investigate the expression of p53 and Beclin1 in salivary pleomorphic adenoma (PA) and its clinical significance. METHODS: The expression of p53 and Beclin1 were assessed by immunohistochemistry in 108 cases of PA and 20 cases of carcinoma in pleomorphic adenoma(CIPA). The results were used to analyze the relationship between gene expressions and the development of PA as well as the clinical pathological features. Statistic analysis was conducted with SPSS 20.0 software package. RESULTS: The positive expressions of p53 in PA samples (9%) were significantly lower than that in CIPA(14%) (P<0.001). The positive expressions of autophagy-related gene Beclin1 in PA samples(91%) were significantly higher than that CIPA (11%) (P<0.001). The expression levels of these genes were not associated with gender, age, clinical course, tumor size, and location of PA(P>0.05). There was a negative correlation between p53 and Beclin1 expression in PA (r=-0.330,P<0.05). CONCLUSIONS: The expression levels of Beclin1 and p53 protein are closely related to the development of PA. Reduced autophagy and enhanced anti apoptosis coexist in the process of tumor formation. Thus, raising the autophagy ability may become another alternative choice for cancer therapy.

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.

[Relationship between P65 and radiotherapy-induced oral squamous cell carcinoma cell line apoptosis].

OBJECTIVE: To investigate the effects of different X-ray doses on the expression of nuclear factor-kappaB (NF-kappaB) P65 in human oral squamous cell carcinoma cell (OSCC) line and the relationship between NF-kappaB P65 and radiation-induced OSCC cell line apoptosis. METHODS: The squamous cell carcinoma of Tca8113 cell was cultivated in the 37 degrees C, 5% CO2 incubator after recovery. The experiment samples were divided into six groups (control group, 2, 4, 6, 8, 10 Gy). After growing to logarithm period, Tca8113 cells were irradiated using above-mentioned X-ray doses. The immunocyteochemistry and Western blot were used to detect the expression of NF-kappaB P65 after irradiation in various times (1, 3, 6, 10, 24, 48 h). The apoptosis rates under different radiotherapy dose were detected by flow cytometer and TDT-mediated dUTP-biotin nick end labeling (TUNEL). RESULTS: Compared with the control group, cytoplasm expression of P65 under different X-ray doses had statistically significant differences (P < 0.05). While the cytoplasm P65 protein expression at different time were compared each other, the 3 h group demonstrated significant difference (P < 0.05). Apoptosis rates in various groups, compared with control group, had statistically significant differences (P < 0.05). While the groups at different time points were compared each other, the apoptosis rates of 3 h group had significant differences (P < 0.05). CONCLUSION: X-ray can activate the NF-kappaB P65 in oral squmaous cell carcinoma cell lines. The correlation between expressional quantity of P65 and radiotherapy induced apoptosis of oral squamous cell carcinoma cell lines possesses positive correlation. The activated and intranuclear P65 may have radiotherapy resistant effect.

[Experimental study on the expression of NF-κB-P65 protein and apoptosis of adenoid cystic carcinoma cells after radiation treatment].

PURPOSE: To detect the expression of p65, a subunit of NF-κB proteins, and apoptosis after adenoid cystic carcinoma cells(ACC-2) irradiated by high energy X-ray, and to investigate the interaction between them. METHODS: ACC-2 cells were cultured and then irradiated by high energy X-ray of different dose(2, 4, 6, 8,10Gy). At the next six time points(1, 3, 6, 10, 24, 48h), the expression of p65 protein in cytoplasm and nucleus was detected by immunocytochemistry and Western blotting. The apoptotic cells were counted by flow cytometry and then observed by TUNEL technique. The data of radiant intensity and apoptotic rate were statistically analyzed by Spearman method with SPSS11.5 software package. RESULTS: In ordinary condition, p65 protein seldom appeared in the nucleus, and mostly stained in the cytoplasm by immunocytochemistry. After irradiation, the protein was observed around the nuclear. Then it went through the nuclear membrane more and more as time going on, finally to the center of the nucleus. The quantity of p65 among the total protein changed gradually after radiation, rising at first, which got to a peak after about 6 to 10 hours, according to the results of Western blotting. At the same time point, p65 protein was found to have a higher expression with a higher dose of irradiation correspondingly. The proportion of apoptotic cells also varied from time to time, and an obvious valley of the apoptotic curve was at the 10th hour after radiation. Compared with the outcome of Western blotting, the results indicated a negative correlation between the apoptotic rate and the radiant intensity or p65 protein expression(P<0.05). CONCLUSIONS: The expression of p65 protein is affected by the irradiation of p65 of high energy X-ray, which is dose-time dependent. The proportion of apoptotic cells decreases as the expression increases.

[Radiosensitization by double suicide gene system in ACC-2 cell].

PURPOSE: To investigate the radiosensitization by prodrug and CD-TK double suicide gene therapy system in adenoid cystic carcinoma cells (ACC-2). METHODS: The eukaryotic expression plasmids pIRES-CD and pIRES-TK were introduced into ACC-2 cells by electroporation. Then ACC-2 cells stably expressing CD and TK gene were obtained by 10-day positive selection with 400 micro g/mL G418 . The total RNA was extracted and the expression of the CD and TK gene in transfected ACC-2 cells was identified by RT-PCR. The positive transfected ACC-2 cells were treated with radiotherapy of different dose (0,2,4,6,8,10 Gy) and prodrug system in aerobic and anoxic condition. Then cell clone formation assay was used to study the radiosensitization by CD-TK double suicide gene therapy and prodrug system in ACC-2.The data was analyzed by multiple factor ANOVA using SPSS11.5 software package. RESULTS: RT-PCR analysis demonstrated that CD and TK genes were effectively expressed in ACC-2 cells. With the increased of X-ray dose, the colony forming rate dropped significantly after radiotherapy. In aerobic condition, the survival fraction of group ACC-2/CD-TK+prodrug were significantly lower than that of group ACC-2 and group ACC-2/CD-TK with the same dose (P<0.05). In anoxic condition, the survival fraction of group ACC-2/CD-TK+pro-drug was significantly lower than that of experimental group ACC-2 and group ACC-2/CD-TK with the same dose (P<0.05). The colony forming rate in aerobic condition was significantly lower than that in anoxic condition of the same cell group and dose. CONCLUSION: The radiosensitivity and the killing effect of X ray to ACC-2 cells can be increased by CD-TK double suicide gene therapy and the prodrug system.

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.

[Construction of recombinant plasmid vector pIRES-CD and its expression in ACC-2 cells].

PURPOSE: To clone CD gene, construct its eukaryotic expression vector pIRES-CD and obtain positive ACC-2 cells expressing E.coli CD gene stably. METHODS: PCR amplification was performed using primers based on E.coli CD gene sequence from Genebank, E.coli genomic DNA as template. PCR product was inserted into pMD18-T. After sequence confirmation, the gene was subcloned to pIRES to construct recombinant eukaryotic expression vector pIRES-CD. Then the combinant plasmid was conducted into ACC-2 cell by electroporation. ACC-2 cells stably expressing CD was obtained by 10-day positive selection with 400 mug/mL G418. Total RNA was extracted and the expression of the CD gene in transfected ACC-2 cells was identified by RT-PCR. RESULTS: PCR yielded a fragment of 1280bp and CD was verified by sequence analysis. A fragment of 6.1kb and inserted fragment of 1280bp were obtained by cutting positive recombinant plasmid of pIRES-CD with XbaI and NotI. RT-PCR analysis demonstrated that CD gene could be effectively expressed in ACC-2 cells. CONCLUSIONS: The CD gene is successfully amplified and the eukaryotic expression plasmid containing E.coli CD is successfully constructed.The positive ACC-2 cell clones expressing CD gene stably are obtained, which provide a basis for further study of adenoid cystic carcinoma gene therapy with CD/5-FC suicide gene system. Supported by Natural Science Foundation of Shandong Province(Grant No.Z2003C03).

[Recovery of infraorbital nerve iujury after middle facial fracture].

PURPOSE: To evaluate the recovery of infraorbital nerve injury after middle facial fracture. METHODS: 28 patients with infraorbital nerve injury were examined in l month, 3 months, 6 months and 12 months after operation by using sharp-blunt test, two-point discrimination,electric pain response test. The data were analyzed with SPSS12.0 software package for Student's t test. RESULTS: 25 cases (25 of 28) with injured nerve recovered normally.The average time of recovery was 25 weeks. The injured nerve didnot recover in 3 of 28. No chronic neuropathic pain was found. CONCLUSIONS: Most nerve dysfunctions following middle facial fracture are reversible and temporary,very few are permanent. If the injured nerve doesn't recover within 6 months, infraorbital nerve decompression may be selected to promote the recovery of the nerve function.

[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.

[The effect of sodium hyaluronate on the rabbit osteoarthrosis].

OBJECTIVE: To study the effect of high-molecular-weight sodium hyaluronate on rabbit osteoarthrosis, which was made by immobilizing the temporomandibular joint. METHODS: 18 common rabbits were equally divided into 2 experimental groups and 1 control group. After the rabbit temporomandibular joint were immobilized, 0.06 ml high-molecular-weight sodium hyaluronate were injected into the left TMJs while the same amount of physiological Saline into the right ones. The animals were terminated after 2 weeks and 4 weeks respectively. The whole bilateral TMJs were removed and histopathological and histochemical examinations were performed to evaluate the changes of articular cartilage and the content of glycansaminoglycan in articular cartilage. RESULTS: There were severe osteoarthrotic changes in the right TMJs, whereas the changes in the left ones were slight. There was a significant difference between them (P < 0.01). CONCLUSION: High-molecular-weight sodium hyaluronate can restrain the degenerative changes of the immobilized TMJs.

[Sphenozygomatic suture as a guide in the reduction of zygomatic fracture].

OBJECTIVE: To investigate the effectiveness of sphenzygomatic suture as a guide in the reduction of zygomatic complex fracture. METHODS: 36 cases of zygomatic complex fracture according to Zingg classification were treated. Reduce sphenozygomatic suture first, then reduce the other fracture line and fixed with titanium micro-plates. Patients were followed up for 4 weeks to 3 months, aesthetic results and X rays symmetry were observed. RESULTS: All patients restored satisfactory facial contour, 35 cases got precise reduction, only 1 patients had slightly discontinued zygomatic arch and infraorbital rim. CONCLUSION: During open reduction of zygomatic fracture, reducing sphenozygomatic suture first, combined with other fracture lines will reconstruct zygomatic complex precisely, and got normal aesthetic outcome.