TLR9 activation induces immunosuppression and tumorigenesis via PARP1/PD-L1 signaling pathway in oral squamous cell carcinoma.

Oral squamous cell carcinoma (OSCC) is the most common type of oral cancer, and metastasis and immunosuppression are responsible for the poor prognosis of OSCC. Previous studies have shown that poly(ADP-ribose) polymerase (PARP)1 plays a key role in the pathogenesis of OSCC. Therefore, PARP1 may serve as an important research target for the potential treatment of OSCC. Here, we aimed to investigate the role of PARP1 in the tumorigenesis of OSCC and elucidate the key molecular mechanisms of its upstream and downstream regulation in vivo and in vitro. In human OSCC tissues and cells, Toll-like receptor (TLR)9 and PD-L1 were highly expressed and PARP1 was lowly expressed. Suppression of TLR9 remarkably repressed CAL27 and SCC9 cell proliferation, migration, and invasion. After coculture, we found that low expression of TLR9 inhibited PD-L1 expression and immune escape. In addition, TLR9 regulated PD-L1 expression through the PARP1/STAT3 pathway. PARP1 mediated the effects of TLR9 on OSCC cell proliferation, migration, and invasion and immune escape. Additionally, in vivo experiments further verified that TLR9 promoted tumor growth and immune escape by inhibiting PARP1. Collectively, TLR9 activation induced immunosuppression and tumorigenesis via PARP1/PD-L1 signaling pathway in OSCC, providing important insights for subsequent in-depth exploration of the mechanism of OSCC.NEW & NOTEWORTHY In this research, we took PARP1 as the key target to explore its regulatory effect on oral squamous cell carcinoma (OSCC). The key molecular mechanisms involved in its upstream and downstream regulation were elucidated in OSCC cell lines in vitro and tumor-bearing mice in vivo, combined with clinical OSCC tissues.

Predictive, preventive, and personalized medicine in breast cancer: targeting the PI3K pathway.

Breast cancer (BC) is a multifaceted disease characterized by distinct molecular subtypes and varying responses to treatment. In BC, the phosphatidylinositol 3-kinase (PI3K) pathway has emerged as a crucial contributor to the development, advancement, and resistance to treatment. This review article explores the implications of the PI3K pathway in predictive, preventive, and personalized medicine for BC. It emphasizes the identification of predictive biomarkers, such as PIK3CA mutations, and the utility of molecular profiling in guiding treatment decisions. The review also discusses the potential of targeting the PI3K pathway for preventive strategies and the customization of therapy based on tumor stage, molecular subtypes, and genetic alterations. Overcoming resistance to PI3K inhibitors and exploring combination therapies are addressed as important considerations. While this field holds promise in improving patient outcomes, further research and clinical trials are needed to validate these approaches and translate them into clinical practice.

Patient-reported outcomes after oral cancer reconstructions with radial and ulnar forearm-free flaps.

OBJECTIVES: This study aimed to evaluate patient-reported quality of life and incidence of decision regret in patients undergoing radial (RFFF) and ulnar forearm-free flaps (UFFF) reconstruction. MATERIALS AND METHODS: Patients undergoing either RFFF or UFFF were assessed with the University of Washington Quality of Life (UW-QOL) and Oral Health Impact Profile (OHIP-14) questionnaires, and the Decision Regret Scale (DRS), both before and at least 12 months post-reconstruction. RESULTS: In total, 40 RFFF and 40 UFFF were included. Harvesting time was longer in RFFF (p = 0.043), and the donor-site defect was significantly larger in RFFF than in UFFF (p = 0.044). Patients with UFFF scored better UW-QOL in the appearance, pain, activity, mood, and social functioning domains (p < 0.05). However, the RFFF group excelled in swallowing and chewing domains. The DRS score revealed a significant difference between RFFF and UFFF, with scores of 36.26 versus 27.36, respectively. Moreover, the mean DRS score reduced at 12 months compared with 6 months, significantly superior for UFFF. CONCLUSION: Oral cancer patients reconstructed with UFFF exhibited a better appearance, social domain, and mild decision regret compared with RFFF, indicating that the UFFF may contribute to improving postoperative quality of life in oral cancer patients.

Oropharyngeal stenosis in patient with oral submucous fibrosis: a case report with 8-year follow-up.

Oral submucous fibrosis (OSF) is a chronic, progressive condition affecting the oral mucosa associated with areca nut consumption. It leads to restricted tongue movement, loss of papillae, blanching and stiffening of the mucosa, difficulty in opening the mouth, and challenges in eating due to inflammation and fibrosis. This report presents a rare case of oropharyngeal stenosis secondary to OSF in a 43-year-old male with a history of chewing betel nut. A surgical procedure similar to Uvulopalatopharyngoplasty was performed to excise the submucous oropharyngeal stenosis and to reconstruct the uvula, palatoglossal arch, and palatopharyngeal arch. At 8 years postoperatively, the patient exhibited a normal mouth opening and oropharyngeal aperture.

Tyrosine sulphation of CXCR4 induces the migration of fibroblast in OSF.

Oral submucous fibrosis (OSF) caused by areca nut chewing is a prevalent fibrotic disease in Asia-Pacific countries. Arecoline-induced migration of fibroblasts (FBs) plays a vital role in the development of OSF. However, the specific molecular mechanisms involved remain unclear. Many studies have shown that tyrosine sulphation of chemokines can influence cell migration. Herein, we demonstrated that arecoline stimulates tyrosine sulphation of the chemokine receptor 4 (CXCR4) through the tyrosylprotein sulphotransferase-1 (TPST-1) to enhance the migration ability of FBs. Moreover, by RNA-Seq analysis, we found that the most significantly altered pathway was the EGFR pathway after the arecoline stimulation for FBs. After the knockdown of arecoline-induced EGFR expression, the tyrosine sulphation of CXCR4 was significantly decreased by the inhibition of TPST-1 induction. Finally, in human OSF specimens, TPST-1 expression was directly correlated with the expression of CXCR4. These data indicate that the arecoline-induced tyrosine sulphation of CXCR4, which is regulated by TPST-1, might be a potential mechanism that contributes to FB migration in OSF.

Lateral approach is a more aesthetical option for radical resection of BSCC: assessment of its surgical, oncological, functional, and aesthetic outcomes.

BACKGROUND: The purpose of this study was to introduce a modified lateral approach for combined radical resection of buccal squamous cell carcinoma (BSCC) and evaluate its surgical, oncological, functional, and aesthetic outcomes in comparison with the conventional lower-lip splitting approach. METHODS: This single-center study retrospectively reviewed 80 patients with BSCC, of which 37 underwent the lateral approach and 43 underwent the conventional approach. Surgical, functional, oncological, and aesthetic evaluations, as well as follow-ups, were recorded and compared. RESULTS: Compared to the conventional approach group, the lateral approach group had a longer surgical time (P = 0.000), but there was no significant difference in other surgical and oncological parameters. Moreover, the scar in the head and neck had a significantly discreet appearance in the lateral approach group, whose satisfaction was better than those in the conventional approach group (P = 0.000). Other oral function parameters, postoperative mouth-opening, and 3-year survival rate were not significantly different between the two groups. CONCLUSION: The lateral approach could provide superior aesthetic results while maintaining equal surgical, functional, and oncological outcomes compared to the conventional approach for radical resection of BSCC.

Oral submucous fibrosis transforming into squamous cell carcinoma: a prospective study over 31 years in mainland China.

OBJECTIVE: Oral submucous fibrosis (OSF) is an oral mucous disease caused by betel quid chewing. It is controversial whether OSF can transform into oral squamous cell carcinoma (OSCC). MATERIALS AND METHODS: In this prospective study, a group of 567 patients with OSF were enrolled from 1986 to 2017 and followed-up until 2019. The cancerous information was collected and analyzed. RESULTS: OSF transformed into OSCC in 32 cases (32/567, 5.6%). The patient's age ranged from 20 to 69 years, and the average age was 52 years. The time taken for transformation ranged from 2 to 24 years, the average being 8.6 years. The cancerous transformation occurred in 18 patients (56%) from years 2 to 9, in 13 patients (41%) from years 10-19 and in 1 patient (3%) from 24 years. We analyzed the betel quid chewing habits and found all 32 patients with OSCC-chewed betel quid. Betel quid chewing was most prevalent in patients aged 40-69 years. Sixteen patients had chewed betel quid for 10-19 years (16/32, 50%) and 19 patients (60%) chewed 10-19 slices each day. The OSCC was located in the left or right buccal regions in 23 patients (23/32; 72%) and in the left or right lingual regions in 4 patients (4/32; 12%). Well, moderately and poorly differentiated squamous cell carcinoma was present in 23 patients (23/32; 72%), 4 patients (3/32; 9%), and 5 patients (5/32; 16%), respectively. CONCLUSION: Our findings supported that OSF is a real oral premalignant disorder. CLINICAL RELEVANCE: The long duration of the transformation from the OSF to OSCC suggests more frequent examinations and corresponding treatments are necessary for OSF patients.

Application of a chimeric ALT perforator flap with vastus lateralis muscle mass in the reconstruction of the defects after radical resection of a buccal carcinoma: A retrospective clinical study.

BACKGROUND AND OBJECTIVES: Aggressive resection of buccal cancer simultaneously leaves both oral and lateral facial defects. It is unknown whether a perforator-based chimeric anterolateral thigh (ALT) flap, with a muscular component, is suitable for the reconstruction of these complicated defects. METHODS: In this retrospective study, 48 patients with a buccal carcinoma (T2 N0-1 M0), who underwent extensive surgical resection, were enrolled. Twenty-seven cases underwent reconstruction using the classical ALT perforator flap (classical group), and 21 cases used the chimeric ALT perforator flap with vastus lateralis muscle mass (chimeric group). The incidence of wound infection, lower limb extremity function, facial appearance, survival curves, and quality of life were compared between groups. RESULTS: The incidence of wound infection or effusion was lower in the chimeric group than in the classical group. The aesthetic result achieved in the chimeric group was better than in the classical group. Meanwhile, there was no significant difference in the function of the donor site between groups. CONCLUSIONS: The chimeric ALT perforator flap, with a muscular component, can reconstruct both the oral and lateral face defects accurately. It sustains the profile of the lateral face and decreases the incidence of wound infection.

Reconstruction for Various Subtypes of Unilateral Buccal Defects After Oncologic Surgery by Using Personalized Anterolateral Thigh Flaps.

PURPOSE: Radical resection of buccal carcinoma frequently leads to intraoral or through-and-through buccal defects. Anterolateral thigh (ALT) flaps can be harvested to reconstruct different buccal defect subtypes. The purpose of this study was to investigate clinical outcomes after the application of personalized ALT flaps for the precise reconstruction of unilateral buccal defects. MATERIALS AND METHODS: Patients with primary unilateral buccal carcinoma who underwent tumor ablation and simultaneous reconstruction of personalized ALT flaps from January 2015 to January 2018 were enrolled in this retrospective case series. Buccal defects were classified into 4 subtypes. Demographic features, defect range and reconstructive method, and perioperative characteristics were reviewed and recorded. Quality of life and mouth opening were assessed by the University of Washington Quality-of-Life questionnaire and interincisal distance (IID), respectively, during follow-up. Descriptive statistics were calculated for each study variable. RESULTS: Four types of ALT flaps were harvested and used to reconstruct different buccal defects in 146 patients. Of the 193 skin paddles applied, 189 survived, and few recipient- and donor-site complications were observed. One hundred eight patients were assessed with the University of Washington Quality-of-Life questionnaire and followed until 12 months postoperatively. Our results showed that physical, functional, social, and emotional domain scores increased steadily during the follow-up period. Ninety-eight patients showed improvements in mouth opening when the IID before the operation was compared with the IID at 3 and 6 months postoperatively. CONCLUSIONS: A personalized ALT flap is a suitable choice for reconstructing unilateral buccal defects after oncologic surgery given its high success rate, customizable and flexible design, low complication rate, and satisfactory esthetic and functional results.

Analysis of risk factors for multiple primary oral squamous cell carcinoma: a cohort study.

OBJECTIVE: Chewing betel quid (CBQ) is popular in Southeast Asia, resulting in a high incidence of oral squamous cell carcinoma (OSCC). The incidence of multiple primary oral cancer (MPOC) has gradually increased and has become one of the main causes of OSCC treatment failure. However, it is unclear whether the high incidence of MPOC is also correlated with the habit of CBQ. MATERIALS AND METHODS: In this retrospective study, 915 OSCC patients were enrolled. MPOC incidence and characteristics were analyzed. CBQ and other risk factors for MPOC were investigated by chi-squared test and logistic stepwise regression analysis. RESULTS: Among 915 patients, 15 were diagnosed with synchronous MPOC. After follow-up, 60 of 915 patients developed a second or third primary lesion site and were diagnosed with metachronous MPOC. The remaining 840 patients were then diagnosed with single primary oral cancer (SPOC). The cumulative incidence of MPOC in all OSCC patients was 8.2%. CBQ and the related oral submucous fibrosis (OSF) were found to be independent risk factors of MPOC (P < 0.001). Both MPOC and SPOC patients with a CBQ habit were much younger than those who did not have a CBQ habit (P < 0.001). The buccal mucosa was the most common primary occurrence site (35.9%) in MPOC cases, and almost all MPOC patients with buccal cancer had previously suffered from OSF (88.9%). CONCLUSION: CBQ and CBQ-related OSF, for the first time, are identified as the independent risk factors of MPOC. Prevention and treatment of OSF as well as cessation of CBQ are expected to become new approaches to reduce the incidence of MPOC. CLINICAL RELEVANCE: More frequent physical examinations should be undertaken in OSCC patients with CBQ or CBQ-related OSF.

Application of chimerical ALT perforator flap with vastus lateralis muscle mass for the reconstruction of oral and submandibular defects after radical resection of tongue carcinoma: a retrospective cohort study.

BACKGROUND: Patients with tongue carcinoma who undergo combined tongue and neck radical resection often have simultaneous oral and submandibular defects. Due to its high flexibility, the anterolateral thigh (ALT) perforator flap is gradually being adopted by surgeons for oral reconstruction. However, the tissue volume of perforator flaps is insufficient for the reconstruction of both the oral and submandibular regions. In this retrospective cohort study, we compared the postoperative outcomes and complications between patients reconstructed with using the classical ALT perforator flap and patients reconstructed using the chimeric ALT perforator flap with vastus lateralis muscle mass. METHODS: From August 2017 to August 2019, 25 patients underwent reconstructive therapy using a classical ALT perforator flap (classical group), while 26 patients were reconstructed with the chimeric ALT perforator flap (chimeric group) after radical resection of tongue cancer in Xiangya Hospital, Central South University. The flap survival rate, incidence of submandibular infection, lateral appearance, lower extremity function, and quality of life were compared between the two groups. RESULTS: There were no differences in flap survival rate and postoperative lower extremity function between the two groups. The incidence of submandibular infection was 15.4 and 40% in the chimeric and classical group, respectively. The duration of recovery was 12.20 ± 2.69 and 15.67 ± 4.09 days in the chimeric and classical group, respectively. The submandibular region fullness was satisfactory in the chimeric group. The postoperative quality of life in the chimeric group was better than that in the classical group (P < 0.05). CONCLUSIONS: The chimerical ALT perforator flap with muscle mass reconstructs both the oral and submandibular defects accurately. It maintains the profile and fullness of the submandibular region and may reduce the incidence of submandibular infection.

Cytotoxic T cell responses to Streptococcus are associated with improved prognosis of oral squamous cell carcinoma.

Several species of Streptococcus, such as S. salivarius, S. mitis, and S. anginosus, are found to extensively colonize the oral cavity and the upper respiratory tract, and have been shown to increase in patients with oral squamous cell carcinoma (OSCC). Accumulating evidence have revealed that commensal bacteria are involved in antitumor immunity via T cell-mediated mechanisms, but the role of Streptococcus enrichment in OSCC is yet unclear. In this study, we stimulated peripheral blood mononuclear cells from non-cancer controls (NCs) and OSCC patients with S. salivarius, S. mitis, and S. anginosus. We observed that compared to NC subjects, OSCC patients at earlier stages had higher frequencies of granzyme B-expressing CD8 T cells for all Streptococcus species tested, while OSCC patients at more advanced stages had higher frequencies of granzyme B-expressing CD8 T cells for S. anginosus but not other Streptococcus species. In OSCC patients, the Streptococcus-reactive CD8 T cells presented significantly lower levels of PD-1 and TIM-3 expression than Streptococcus-nonreactive CD8 T cells. The clinical outcomes of OSCC patients in our cohort were tracked for 24 months after the resection of the primary tumor. In patients that did not present tumor recurrence, the frequencies of S. salivarius-reactive and S. mitis-reactive CD8 T cells were significantly higher than that in patients that developed recurrent tumor. Furthermore, in patients with tumor recurrence, the duration between primary tumor resection and tumor recurrence was positively associated with the frequencies of S. salivarius-reactive and S. anginosus-reactive CD8 T cells. Together, we demonstrated that Streptococcus-reactive CD8 T cell responses might contribute to antitumor immunity in OSCC patients.

Streptococcus salivarius-mediated CD8+ T cell stimulation required antigen presentation by macrophages in oral squamous cell carcinoma.

It has been shown that the peripheral blood mononuclear cells (PBMCs) from oral squamous cell carcinoma (OSCC) patients presented cytotoxic CD8 T cell response against Streptococcus salivarius (S. salivarius), of which the frequency was positively associated with recurrence-free survival in OSCC patients. To identify the conditions required for regulating S. salivarius-specific CD8 T cell-mediated cytotoxicity, we selectively depleted individual components of the PBMCs, and observed that the depletion of monocytes/macrophages, but not other immune cell subsets, significantly downregulated the S. salivarius-specific CD8 T cell cytotoxicity. Monocyte/macrophage alone was sufficient to reconstitute optimal granzyme B expression from S. salivarius-specific CD8 T cells. Also, both the memory and the naive CD8 T cells reacted to S. salivarius-stimulation, with the memory CD8 T cells presenting significantly higher S. salivarius-reactivity. Using M1- and M2-polarized macrophages from circulating monocytes, we found that M1-polarized macrophages, with significantly higher IL-12 expression and significantly lower IL-10 and MHC class II molecule expression, was more effective at promoting granzyme B responses in CD8 T cells, and required CD80/CD86 costimulating molecules for optimal responses. Interestingly, the tumor-associated macrophages (TAMs) from resected tumors presented characteristics of M2-polarized macrophages with high MHC class II expression and low IL-12 secretion. The frequency of tumor-infiltrating S. salivarius-specific cytotoxic CD8 T cell was inversely correlated with the level of IL-10 secretion and the MHC class II molecule expression in autologous TAMs. Together, we demonstrated that monocyte/macrophages presented essential antigen-presentation and costimulatory roles in CD8 T cell-mediated S. salivarius-specific granzyme B responses, and the polarization of macrophages could influence the potency of CD8 T cell responses.

Pathogenesis investigation of miR-199-5p in oral submucous fibrosis based on bioinformatics analysis.

OBJECTIVES: Fibrosis diseases are one of the leading causes of suffering and death. However, no systematic investigation has been carried out on fibrosis-related genes. MATERIALS AND METHODS: By querying PubMed using keywords "fibrosis" and "gene" or "protein," we identified fibrosis-related genes in the last decade. Bioinformatics analysis was performed by MAS 3.0 software. Key miRNA was selected to assess its relationship with oral submucous fibrosis (OSF) and fibroblast functions. RESULTS: A total of 1,310 genes related to fibrosis were identified. TGF-ß1, CTGF, MMP9, HSP47, and S1P were found to be associated with mainly fibrotic organs. In total, 244 cellular components terms, 595 molecular function terms, 1,816 cellular component terms, and 136 KEGG pathway annotations were predicted. miR-199-5p was selected as the key miRNA, which has higher level in OSF. Upregulated miR-199-5p was significantly related to OSF duration and OSF histological grade (p = 0.028 and 0.012, respectively). Overexpressive miR-199-5p reduced proliferation and induced apoptosis in buccal fibroblasts. Additionally, expression levels of collagen I (COL I) and III (COL III) were promoted by overexpressive miR-199-5p in buccal fibroblasts. CONCLUSION: These results indicate that fibrosis-related genes are related to a series of complex mechanisms. The characteristics of miR-199-5p may supply important clues for developing therapeutic strategy for OSF.

Functional Mandibular Reconstruction With Double-Barrel Fibular Flap and Primary Osseointegrated Dental Implants Improve Facial Esthetic Outcome.

PURPOSE: Osseointegrated dental implants in fibular free flaps can be used to reconstruct segmental mandibular defects resulting from head and neck resections. The double-barrel fibular flap (DBFF) has been applied as a modified method to overcome insufficient fibular width. This article describes the use of the DBFF with simultaneous dental implant placement as a superior method for esthetic mandibular reconstruction. MATERIALS AND METHODS: From 2012 to 2015, 26 patients underwent mandibular reconstruction with a free fibular flap and immediate dental implant placement after segmental mandibulectomies. Twelve patients received the DBFF and the other 14 patients received the conventional single-barrel fibular flap (SBFF). Palatal mucosal grafting was performed when necessary. Functional and esthetic outcomes were evaluated after 31 to 45 months of follow-up. RESULTS: All microvascular fibula transplantations were successful. All patients completed prosthodontic rehabilitation. The mean follow-up of patients after reconstruction was 36.3 months (range, 31 to 45 months). The facial esthetic score was significantly higher in patients treated with the DBFF than with the SBFF after 24 and 30 months (P < .05). There was no significant difference in marginal bone resorption between the DBFF and SBFF groups (P > .05). CONCLUSIONS: This 1-stage surgical method is safe and reliable. Use of the DBFF markedly decreased the height discrepancy between the native and new mandible and achieved a better lower face esthetic outcome than the SBFF. Osseointegrated dental implantation was adequate to achieve satisfactory dental rehabilitation in the DBFF group.

SCAPs Regulate Differentiation of DFSCs During Tooth Root Development in Swine.

The tooth root transmits and balances occlusal forces through the periodontium to the alveolar bone. The periodontium, including the gingiva, the periodontal ligament, the cementum and the partial alveolar bone, derives from the dental follicle (DF), except for the gingiva. In the early developmental stages, the DF surrounds the tooth germ as a sphere and functions to promote tooth eruption. However, the morphological dynamics and factors regulating the differentiation of the DF during root elongation remain largely unknown. Miniature pigs are regarded as a useful experimental animal for modeling in craniofacial research because they are similar to humans with respect to dentition and mandible anatomy. In the present study, we used the third deciduous incisor of miniature pig as the model to investigate the factors influencing DF differentiation during root development. We found that the DF was shaped like a crescent and was located between the root apical and the alveolar bone. The expression levels of WNT5a, ß-Catenin, and COL-I gradually increased from the center of the DF (beneath the apical foramen) to the lateral coronal corner, where the DF differentiates into the periodontium. To determine the potential regulatory role of the apical papilla on DF cell differentiation, we co-cultured dental follicle stem cells (DFSCs) with stem cells of the apical papilla (SCAPs). The osteogenesis and fibrogenesis abilities of DFSCs were inhibited when being co-cultured with SCAPs, suggesting that the fate of the DF can be regulated by signals from the apical papilla. The apical papilla may sustain the undifferentiated status of DFSCs before root development finishes. These data yield insight into the interaction between the root apex and surrounding DF tissues in root and periodontium development and shed light on the future study of root regeneration in large mammals.

Tripaddled Anterolateral Thigh Flap for the Reconstruction of Extensively Full-Thickness Cheek Defects by Stacking Two Skin Paddles as Kiss Pattern.

Extended anterolateral thigh (ALT) flap can provide a large amount of skin to reconstruct the extensively full-thickness defects of cheek. However when the width of 1 skin paddle exceeds 8 cm, it always results in that the donor site cannot be closed primarily and need to be covered by split-thickness skin grafting, which delivers lots of impacts on the functional and cosmetic outcome of the thigh. The aim of this study was to introduce the authors' modification of stacking 2 skin paddles of the tripaddled ALT flap to reconstruct the extensive full-thickness defects in the cheek after the radical ablasion of advanced buccal squamous cell carcinoma. Ten patients of advanced buccal squamous cell carcinoma between March 2014 and December 2016 were enrolled in the authors' hospital. All the patients were received the soft-tissue reconstructions for the extensively full-thickness cheek defects by using the tripaddled ALT chimeric flaps. Among 3 skin paddles, the distal paddle was used to reconstruct the inner mucosa defect, and the other 2 large skin paddles were stacked side by side for outer mega cheek defect. The mean area of the intraoral defect was 32.2 cm and the mean area of the extraoral defect was 106.34 cm. The mean width of the outer skin defect was 9.5 cm. All the flaps survived and all the donor sites were closed primarily. So, stacking 2 skin paddles of a tripaddled ALT flap as a kiss pattern is a novel modification on conventional flap design to provide customized coverage for extensive and full-thickness buccal defects while minimizing donor-site morbidity.

Application of Combined Osteotomy and Reconstruction Pre-Bent Plate Position (CORPPP) Technology to Assist in the Precise Reconstruction of Segmental Mandibular Defects.

PURPOSE: To introduce and evaluate the clinical effects of digital surgical guide plate technology in the combined osteotomy and reconstruction pre-bent plate position (CORPPP) technique during mandibular segmental resections. MATERIALS AND METHODS: Seven cases of mandibular segmental resection with simultaneous vascularized free fibula flap reconstruction by oral and maxillofacial surgery were selected (Xiangya Hospital, Changsha, China; June 2015 through December 2015). Cone-beam computed tomographic (CBCT) and spiral CT scans of mandibles and fibular donor sites, respectively, were collected. Surgical simulations were conducted after data collection. Pre-bent titanium plates were placed within the predicted mandibular models. The samples were scanned by CBCT to obtain the positional relations. Then, CORPPP surgical guide plates with location holes were designed and fabricated on pre-bent titanium plates. The CORPPP surgical guide plates were applied in osteotomy and the placement of pre-bent titanium plates during surgery. CBCT scans were obtained 2 weeks after surgery to examine the reconstructed composite models composed of mandibles and titanium plates. Then, the scans were compared with the preoperatively designed models. In addition, the deviation of the integral and characteristic structure loci was analyzed. RESULT: The 7 cases with placed pre-bent titanium plates exhibited good recovery in occlusal relations and the contour of the reconstructed mandibles. The absolute deviations in the integral analysis were 0.89 ± 0.96 mm (mandibles) and 0.33 ± 0.36 mm (titanium plates). The absolute deviations on the diseased side were 1.78 ± 0.35 mm (condylar head), 2.43 ± 0.29 mm (gonion), 2.22 ± 0.22 mm (gnathion), and 2.66 ± 0.36 mm (mesial inferior margin of the fibula). CONCLUSION: The results of this study suggest that mandibular segmental resections and the precise orientation of pre-bent titanium plates could be simultaneously assisted by CORPPP digital surgical guide plates. The use of these guide plates should be expanded.

Vascularized Fascia Lata for Prevention of Postoperative Parotid Fistula Arising From Partial Parotidectomy During Neck Dissection.

PURPOSE: Postoperative parotid fistula can occur after partial parotidectomy, which is a routine surgical procedure during neck dissection of oral cancers arising from or close to the oropharyngeal area. The aim of this study was to evaluate the reliability of vascularized fascia lata for the prevention of postoperative parotid fistula after neck dissection. MATERIALS AND METHODS: A retrospective review was conducted of patients with oral cancer who underwent ablative resection involving the parotid tail and reconstruction using the anterolateral thigh (ALT) flap with a vascularized fascia lata paddle. The vascularized fascia lata paddle was used to seal off the parotid stump by tightly suturing the edges of the fascia lata and parotid wound together. RESULTS: Twenty-three patients (18 men and 5 women) with primary oral cancer arising from or close to the oropharyngeal area were enrolled. The mean area of parotid defect was 16.7 cm2 and the mean area of fascia lata harvested was 21.8 cm2. All flaps survived. Pressure dressing or anticholinergic drugs were not used in any case. During the follow-up period, there was no clinical evidence of the development of parotid fistula. CONCLUSION: The vascularized fascia lata paddle is a reliable option for the prevention of postoperative parotid fistula after neck dissection of oral cancer.

Quantitative proteomic analysis for novel biomarkers of buccal squamous cell carcinoma arising in background of oral submucous fibrosis.

BACKGROUND: In South and Southeast Asian, the majority of buccal squamous cell carcinoma (BSCC) can arise from oral submucous fibrosis (OSF). BSCCs develop in OSF that are often not completely resected, causing local relapse. The aim of our study was to find candidate protein biomarkers to detect OSF and predict prognosis in BSCCs by quantitative proteomics approaches. METHODS: We compared normal oral mucosa (NBM) and paired biopsies of BSCC and OSF by quantitative proteomics using isobaric tags for relative and absolute quantification (iTRAQ) to discover proteins with differential expression. Gene Ontology and KEGG networks were analyzed. The prognostic value of biomarkers was evaluated in 94 BSCCs accompanied with OSF. Significant associations were assessed by Kaplan-Meier survival and Cox-proportional hazards analysis. RESULTS: In total 30 proteins were identified with significantly different expression (false discovery rate < 0.05) among three tissues. Two consistently upregulated proteins, ANXA4 and FLNA, were validated. The disease-free survival was negatively associated with the expression of ANXA4 (hazard ratio, 3.4; P = 0.000), FLNA (hazard ratio, 2.1; P = 0.000) and their combination (hazard ratio, 8.8; P = 0.002) in BSCCs. CONCLUSION: The present study indicates that iTRAQ quantitative proteomics analysis for tissues of BSCC and OSF is a reliable strategy. A significantly up-regulated ANXA4 and FLNA could be not only candidate biomarkers for BSCC prognosis but also potential targets for its therapy.