Tracking the dropout patients of neoadjuvant chemotherapy with locally advanced oral cavity cancer.

BACKGROUND: Patients with locally advanced oral cavity cancer sometimes stopped treatment after neoadjuvant chemotherapy. There are no guidelines of the management for these patients. Before designing clinical trials, we conducted this study to investigate their characteristics, reasons of dropout, and the follow-up information. METHODS: Medical records were consecutively reviewed of patients with locally advanced oral cavity cancer who underwent neoadjuvant chemotherapy from Jan 2017 to Dec 2019.Variables were compared between patients stopped treating after chemotherapy and completed treatments by student t-test and Chi-square test. Logistic regression model was used to calculate the odd rations of potential predictors of dropout. The dropout patients were followed up for reasons and results of their decision. RESULTS: A total of 171 patients were included with 23 not undergoing surgery after chemotherapy. The odd ratios of age over 65 and single marital status were 3.11 (95%CI: 1.1, 8.7) and 4.935 (95%CI: 1.5, 16.1), respectively, for the dropout. The median survival of patients without surgery was 7.4 months. Believing that chemotherapy would be effective and being afraid of the consequence of surgery were the main reasons of refusing surgery. CONCLUSIONS: The prognosis was poor of these dropout patients. Symptom relief and fear of surgery were the reasons of dropout. Age and marital status affected their decision. Clinical trials are needed to be designed for these patients.

Assessing the magnetic resonance imaging in determining the depth of invasion of tongue cancer.

OBJECTIVES: To assess the magnetic resonance imaging (MRI) in predicting tumour's depth of invasion (DOI) of tongue cancer by comparing to pathology and to determine the cut-off value of MRI-derived DOI for lymph node metastasis. PATIENTS AND METHODS: In a retrospective analysis, 156 patients with newly diagnosed tongue cancer were included. Tumour's DOI was compared between MRI measurement and pathology by Pearson correlation coefficient and paired t test. The accuracy of MRI-derived DOI was compared to the pathological DOI. The relationship between MRI-derived DOI and cervical lymph node metastasis was calculated by receiver operating characteristic curve. RESULTS: Tumour's DOI was well correlated between MRI measurement and pathology with correlation coefficients of 0.77. MRI-derived DOI was 3.4 mm (28%) larger than pathology. The accuracy of MRI in deciding pathological DOI was 67.9%. The cut-off value of MRI-derived DOI was 10.5 mm for lymph node metastasis of tongue cancer. CONCLUSION: Magnetic resonance imaging can be used as a reference to determine tumour's DOI of tongue cancer. Tumour with MRI-derived DOI larger than 10.5 mm deserves simultaneous neck dissection at initial surgery.

A Novel Laryngoscope-assisted Method for Sealing Pharyngocutaneous Fistula.

ABSTRACT: Pharyngocutaneous fistula (PCF) is one of the most common but stranded complications for salvage laryngectomy. As for localized fistula, there is no convincing standard and method to cure. This paper described a patient who was submitted to extensive resection of mass in right lingual root, total laryngectomy, and pharyngoesophageal reconstruction with an anterolateral thigh flap (ALTF), because of recurred carcinoma of right lingual root which invaded bilateral epiglottis. 2 weeks after surgery, subsequent pharyngocutaneous fistula developed at the junction of the tracheostomy, and maintained over 2 months under conservative treatment. With the assistance of laryngoscope, inner and outer orificiums of fistula were found and sealed by bundled iodoform strip. 9 days after sealing, fistula had been already filled with fresh granulation tissue. During 2 years after surgery, the fistula area dose not recur. This technique provides a safe and effective way for sealing the inner and outer orificiums of fistula.

High-risk lymph node ratio predicts worse prognosis in patients with locally advanced oral cancer.

BACKGROUND: To investigate the prognostic value of lymph node ratio (LNR), as well as the correlation with docetaxel, cisplatin, and 5-FU (TPF) induction chemotherapy, in patients with locally advanced oral squamous cell carcinoma (OSCC). METHODS: Two-hundred and forty-five patients from a phase 3 trial involving TPF induction chemotherapy in stage III/IVA OSCC patients (NCT01542931) were enrolled in this study between 2008 and 2010. The clinical and pathological data were collected and analyzed. The cutoff value for LNR was calculated on the receiver operating characteristic (ROC) curve. Univariate and multivariate Cox regression models, and Kaplan-Meier method were used for survival analysis. RESULTS: According to the ROC curve, the cutoff value for LNR was 7.6%. With a median follow-up period of 80 months, the OSCC patients with high-risk LNR (> 7.6%), or positive extranodal extension (ENE) had significantly worse clinical outcomes than patients with low-risk LNR (≤7.6%) or negative ENE. Multivariate analysis on pathological covariates showed that only high-risk LNR was an independent negative predictive factor for survival (P < .05). The cutoff value of LNR of 7.6% was also verified with the similar results using an open TCGA database, high-risk LNR indicating worse overall survival (P < .001) and disease-free survival (P < .001). CONCLUSION: Oral squamous cell carcinoma patients with high-risk LNR have a worse clinical outcome than patients with low-risk LNR. High-risk LNR is an independent negative predictive factor for clinical outcome in patients with locally advanced OSCC.

Salivary gland carcinoma in Shanghai (2003-2012): an epidemiological study of incidence, site and pathology.

BACKGROUND: Salivary gland carcinoma ranks the sixth in head and neck cancers while it is relatively rare in its incidence. Epidemiological studies have been based mostly on institutional data, leading to selection bias in incidence evaluation. Most population-based cancer registries have grouped cancers of the minor salivary glands with oral cancer instead of with salivary gland carcinoma as a whole, because of the international disease coding. Thus, the incidence of salivary gland carcinoma has not been well assessed. The aim of the study is to evaluate the incidence of both minor and major salivary gland cancers in Shanghai during the years 2003-2012, and to analyse the site and histological distributions. METHODS: Data from the Shanghai Cancer Registry system were extracted for patients diagnosed with malignancies of the major or minor salivary glands for the year 2003 to 2012. Pertinent socio-demographic data were obtained from the Shanghai Municipal Bureau of Public Security. The age-standardized incidence rates were calculated directly according to the world standard population. The change in incidence during the study period was analysed by comparing the rates during the first and next five years. The distributions of anatomic subsites and histology were also analysed. RESULTS: A total of 1831 cases were identified, representing 0.35% of all malignancies during the study period. The median age was 59 and 57 years for men and women, respectively. The age-standardized incidence was 7.99 per 1,000,000 person-year, with a male-to-female ratio of 1.10. There was no significant change in the incidence during the 10-year period. The anatomic distribution confirmed the 4:1:2 rule for the parotid, submandibular, and minor glands. In men, adenocarcinoma not otherwise specified was the most common histological type followed by mucoepidermoid; in women, the mucoepidermoid was the most common histotype, followed by the adenoid cystic. CONCLUSION: Salivary gland carcinoma is relatively rare in incidence. However, the variations in age and sex distribution in sites and histology types suggest differences in aetiology which warrants further investigation.

Clinical Application of Temporary External Fixator for Immediate Mandibular Reconstruction.

Immediate mandibular reconstruction is always necessary for the patients receiving segmental mandibulectomy to recover the facial contour and function of occlusion. When 3D modeling is unavailable, temporary external fixator is necessary to maintain the occlusion relationship and facial contour. In this study, we introduce the clinical application of temporary external fixator for immediate mandibular reconstruction in patients receiving segmental mandibulectomy, which consists of 2 anchor claws, 2 all-round retentive arms, and 1 central locking structure. From August 2016 to September 2017, temporary external fixator was applied in 13 patients. Clinical data of gender, age, surgical procedure, duration of operation, and clinical outcomes were recorded and analyzed. Among the 13 patients, there were 4 men and nine women whose ages ranged from 21 to 64 (mean 47.7) years old. There were 9 benign and 4 malignant lesions. All lesions expended at the buccal side of mandible. 12 fibular flaps and 1 vascularized iliac bone graft were used. The mandibular defect ranged from 6 to 14 (mean 10) cm. The operation duration of surgery ranged from 5 to 10 (mean 7) hours. All flaps survived with primary healing. The occlusion and facial contour were good, without significant changes of the length of mandibular body and width of mandible before and after surgery. No functional sequelae were noted at the donor sites. From these results, the temporary external fixator is easy to operate; the surgical procedure is simple and time-saving for surgeon when 3D modeling is unavailable. The indication for temporary external fixator usage is the mandibular lesion growing outward to cheek soft tissue.

Oral cancer incidence in Shanghai ---- a temporal trend analysis from 2003 to 2012.

BACKGROUND: Oral cancer is a serious problem owing to its poor prognosis and destruction of patients' eating ability as well as facial appearance. Epidemiological studies can provide aetiological clues for prevention. The prevalence of oral cancer in densely populated cities in eastern China is unclear. The aim of the study is to analyse the incidence rates of oral cancer in Shanghai over the period 2003-2012 and estimate the temporal trends. METHODS: Cases of oral cancer were retrieved from the Shanghai Cancer Registry system in the Shanghai Municipal Center for Disease Control & Prevention for the years 2003 to 2012. Information on the corresponding population was obtained from the Shanghai Municipal Bureau of Public Security. Age-standardised incidence rates were directly calculated according to the world standard population. An annual percent change model was employed to analyse the temporal trends of cancer incidence. RESULTS: A total of 3860 oral cancer cases were reported, representing 0.69% of all malignancies in Shanghai during the 10-year study period. The mean age at diagnosis was 64 years. The age-standardised incidence rate was 1.34 per 100,000 person-years, with a male-to-female ratio of 1.41. Annually, the incidence rates increased by 3.83 and 2.54% for men and women, respectively. The increase was most noticeable in males aged 45-64 years. CONCLUSION: In Shanghai, the oral cancer incidence is relatively low. However, it is continuously increasing, especially among middle-aged males. This finding urges further investigations on the risk factors of oral cancer in this population, especially on changes in living patterns, such as the smoking, drinking, and dietary habits.

PDGFRA mRNA overexpression is associated with regional metastasis and reduced survival in oral squamous cell carcinoma.

BACKGROUND: Platelet-derived growth factor alpha (PDGFRA) is a gene encoding tyrosine kinase receptor and both EGFR and PDGFRA activate tyrosine kinases. The implication of PGFRA in many cancers and its prognostic significance irrespective to EGFR status in spinal chordoma, gliomas, and uterine cancers have shown a need for its investigation in oral squamous cell carcinoma (OSCC). We investigated the prognostic value of PDGFRA mRNA expression in OSCC. PATIENTS AND METHODS: The study was conducted in the department of oral maxillofacial surgery-head and neck oncology, at a tertiary hospital. The data on PDGFRA mRNA expression and immunohistochemical staining status in primary OSCC patients treated for curative surgery from 2010 to 2012 were analyzed. Univariate and multivariate analyses were performed with other cofactors for survival. RESULTS: A total of 114 consecutive patients with primary OSCC who received treatment were studied. Thirty-one patients died of the disease. Strong PDGFRA immunohistochemical staining and high expression of PDGFRA mRNA were associated with positive pN status (P < .001), disease-free survival (P < .001), and overall survival (P < .001) in multivariate cox regression when all other factors such as pN status and histological grading were analyzed. Kaplan-Meier analysis revealed that the 2-year survival and 3-year survival of patients with PDGFRA mRNA low expression were 96.83%. However, 2-year survival for PDGFRA mRNA high expression level was 59.64%, which decreased to 45.57% by 3-years. CONCLUSION: PDGFRA overexpression in oral SCC, in respect to strong PDGFRA immunohistochemical staining and high PDGFRA mRNA expression, was positively associated with regional metastasis and reduced patient survival.

Proper Choice of Donor Site Veins for Patients Undergoing Free Radial Forearm Flap Reconstruction for the Defects of Head and Neck.

PURPOSE: The purpose of this study was to analyze the reliability of the deep venous drainage system of the free radial forearm flap. MATERIALS AND METHODS: The authors implemented a retrospective cohort study and enrolled patients admitted for the evaluation and management of head and neck tumors with radial forearm flap reconstruction. The primary predictor variables were the donor site veins, including the deep, dual, and superficial venous drainage systems. The primary outcome measurement was the incidence of venous compromise. Potential confounders included patient demographics, history of chemotherapy with or without radiotherapy, defect sites, and the recipient artery and vein. The χ2 test and logistic regression analysis were used for statistical analysis. RESULTS: The final study population consisted of 520 patients (mean age, 54 years) who underwent head and neck soft tissue reconstruction using the free radial forearm flap. Patients with the deep system (odds ratio [OR] = 0.251; 95% confidence interval [CI], 0.108-0.581) or dual system (OR = 0.197; 95% CI, 0.064-0.605) had a markedly lower risk of venous compromise than those with the superficial system. The overall incidence of inadequate outflow was 2.5% (5 of 204) when the deep system was used alone and 8.9% (19 of 212) when the superficial system was used alone (P = .004). CONCLUSIONS: Patients with the deep venous drainage system had a statistically lower risk of venous compromise. This study recommends using the deep system as a drainage vein for the free radial forearm flap.

PDGFRA mRNA is overexpressed in oral cancer patients as compared to normal subjects with a significant trend of overexpression among tobacco users.

BACKGROUND: Platelet-derived growth factors alpha (PDGFA) is a tyrosine kinase receptor activator which is known to be amplified in the malignancies, and their expression levels are correlated to tumor progression and reduced overall survival. The expression of PDGFRA is different among the tumors and normal tissues; furthermore, their expression level is site specific. Under a physiological condition, PDGFRA and its ligand are expressed in distinct cell populations and activated in a paracrine manner. Nevertheless, heterodimer characteristic of PDGFRA allows it to be trans-activated by non-specific ligands or via autocrine manner. The future of cancer therapy can be based on PDGFRA receptor blockade and therefore warrants further investigation to determine the differing expression of PDGFRA between controls and patients with oral squamous cell carcinoma (OSCC). METHODS: We performed a case-control study of 111 patients with newly diagnosed tongue squamous cell carcinoma and 111 control subjects without a cancer diagnosis, matched for age and gender, to evaluate the association between PDGFRA expression levels in oral mucosa. We then performed smoking stratification in each cohort. Independent t test analysis was applied for case-control comparisons. RESULTS: Mean value of PDGFRA mRNA level (-ΔCt) for normal cohort is -30.242, whereas mean value of PDGFRA mRNA level for patients with OSCC is -11.516. PDGFRA mRNA level (-ΔCt) was significantly higher in oral cancer cohort, P<.001. Smokers have a significantly higher PDGFRA mRNA expression in comparison with non-smokers (P=.002) among the non-cancer group. Likewise, this trend is observed in cancer cohort too, P=.044. CONCLUSION: PDGFRA expression is significantly higher in oral cancer cohort with or without the establishment of tobacco risk factor.

Low Pretreatment Lymphocyte-Monocyte Ratio and High Platelet-Lymphocyte Ratio Indicate Poor Cancer Outcome in Early Tongue Cancer.

PURPOSE: The white blood cell (WBC) indices have been reported to have a prognostic impact in cancer of multiple organs including head and neck cancer; however; site and stage stratification was not attempted, and compelling evidence has shown that early cancers have a different distribution and prognostic ability than late-stage cancers. We studied the prognostic importance of WBC indices in early oral tongue cancers. PATIENTS AND METHODS: The retrospective data of primary pT1N0 to pT2N0 oral tongue cancers treated between 2009 and 2013 were charted. WBC indices such as the neutrophil count, lymphocyte count (LC), platelet count (PC), and monocyte count, along with derived indices such as the neutrophil-lymphocyte ratio, platelet-lymphocyte ratio (PLR), and lymphocyte-monocyte ratio (LMR), were analyzed by multivariate analysis with other clinicopathologic prognostic factors. RESULTS: A total of 133 patients fulfilled the inclusion criteria; the minimum follow-up period for living patients was 36 months. A total of 22 patients reported disease relapse, and 11 patients died of disease. Multivariate analysis showed LC (hazard ratio [HR], 0.206; 95% confidence interval [CI], 0.092 to 0.46; P < .001), PC (HR, 1.011; 95% CI, 1.001 to 1.021; P = .026), PLR (HR, 1.012; 95% CI, 1.008 to 1.016; P < .001), and LMR (HR, 0.721; 95% CI, 0.596 to 0.872; P = .001) are significant independent prognostic factors for disease-free survival. Distant metastasis (HR, 9.014; 95% CI, 2.303 to 38.914; P = .004), LC (HR, 0.091; 95% CI, 0.015 to 0.558; P = .01), PC (HR, 1.023; 95% CI, 1.006 to 1.041; P = .009), PLR (HR, 1.016; 95% CI, 1.004 to 1.027; P = .002), and LMR (HR, 0.58; 95% CI, 0.387 to 0.868; P = .008) are significant independent prognostic factors for overall survival. CONCLUSIONS: Low pretreatment LMR and high PLR indicate poor survival in patients with early tongue cancer. We suggest close follow-up for this subgroup despite radical resection with clear margins.

XL413, a cell division cycle 7 kinase inhibitor enhanced the anti-fibrotic effect of pirfenidone on TGF-ß1-stimulated C3H10T1/2 cells via Smad2/4.

Pirfenidone is an orally bioavailable synthetic compound with therapeutic potential for idiopathic pulmonary fibrosis. It is thought to act through antioxidant and anti-fibrotic pathways. Pirfenidone inhibits proliferation and/or myofibroblast differentiation of a wide range of cell types, however, little studies have analyzed the effect of pirfenidone on the mesenchymal stem cells, which play an important role on the origin of myofibroblasts. We recently found that pirfenidone had anti-proliferative activity via G1 phase arrest and cell division cycle 7 (Cdc7) kinase expression decrease in transforming growth factor-ß1 (TGF-ß1)-stimulated murine mesenchymal stem C3H10T1/2 cells. Pirfenidone also had inhibiting effect on the migration and α-SMA expression. Moreover, in this study we showed for the first time that Cdc7 inhibitor XL413 enhanced the anti-fibrotic activity of pirfenidone via depressed the expression of Smad2/4 proteins, and also prevented the nuclear accumulation and translocation of Smad2 protein. In conclusion, we demonstrated that pirfenidone inhibited proliferation, migration and differentiation of TGF-ß1-stimulated C3H10T1/2 cells, which could be enhanced by Cdc7 inhibitor XL413, via Smad2/4. Combination with pirfenidone and XL413 might provide a potential candidate for the treatment of TGF-ß1 associated fibrosis. It needs in vivo studies to further validate its therapeutic function and safety in the future.

Clinical Application of an Original Vascular Anastomosis: A Clinical Multicenter Study.

PURPOSE: Vascular anastomosis is the most important technical step required for the possibility of free tissue transfer, and mismatch of the donor and recipient vessel size is the most common surgical challenge. As recent reports have described a new method (Ren anastomosis) to resolve this challenge, the goal of this study was to assess these newly described microvascular anastomosis methods. PATIENTS AND METHODS: The study was conducted at 2 institutes in China in different periods. Patients were recruited from the Second Xiangya Hospital between February and May 2013 and from the Shanghai Ninth People's Hospital between March and May 2015. All patients who participated in this study needed free flaps for oral and maxillofacial defects. Patients were divided into the experimental group and the control group. In the experimental group, isometric double-notch end-in-end microvascular anastomosis (Ren anastomosis) was performed, whereas end-to-end anastomosis was performed in the control group. Statistical differences were assessed by use of χ2 and t tests. RESULTS: A total of 148 patients (108 men and 40 women) were treated over the course of this study. There was a statistically significant difference (P < .001) in the operation time for the microscopic artery anastomosis between the experimental group (70 cases; 5.6 ± 1.8 minutes) and the control group (78 cases; 14.6 ± 3.7 minutes). In each group, 1 case of artery compromise was observed. CONCLUSIONS: The Ren anastomosis was time-saving, straightforward, efficient, and easy to learn, with a high patency rate.

Elevated level of serum growth differentiation factor 15 is associated with oral leukoplakia and oral squamous cell carcinoma.

BACKGROUND: Although molecular mechanism of growth differentiation factor 15 (GDF15) in tumorigenesis of oral squamous cell carcinoma (OSCC) is not clear, the diagnostic and prognostic value of serum GDF15 detection has been noticed. However, serum GDF15 levels in patients with oral leukoplakia and GDF15 as a potential predictive biomarker for response to induction chemotherapy in patients with OSCC have not been reported. METHODS: Pretreatment serum GDF15 concentration was detected using an enzyme-linked immunosorbent assay in 30 healthy persons, 24 patients with oral leukoplakia, and 60 patients with OSCC. RESULTS: Serum GDF15 concentration was significantly higher in patients with oral leukoplakia and OSCC, compared with healthy controls (F = 13.701, df = 2, P < 0.001). From a diagnostic standpoint, a cutoff value of 346.9 ng/l of serum GDF15 concentration was calculated using receiver operating characteristic curve, with a sensitivity of 0.750, specificity of 0.867, Youden's Index of 0.617, and area under curve of 0.863. From a prognostic standpoint, patients with serum GDF15 concentration <346.9 ng/l had an improved 3-year disease-free survival rate (64.3% vs 56.5%) compared with those above 346.9 ng/l, but the difference was not statistically significant. A decreased concentration of GDF15 (<346.9 ng/l) showed a predictive trend toward an improved response to induction chemotherapy compared with elevated concentration with clinical response rates of 100% and 71.4%, respectively, but the difference was not significant. CONCLUSION: Elevated GDF15 level may be not only a diagnostic biomarker for oral leukoplakia, but also a prognostic/predictive biomarker associated with decreased survival and diminished response to induction chemotherapy for patients with OSCC.

A new clinical manifestation for cheek alveolar soft-part sarcoma: a case report and review of the literature.

Alveolar soft part sarcoma (ASPS) is a rare, histologically distinct, soft tissue malignancy with nonspecific clinical features usually described as a nonulcerated, painless, expanding mass. It has a pseudoalveolar appearance with clustered polygonal cells lacking central cohesion. It accounts for approximately 0.5 to 1% of all soft tissue sarcomas. It has a strong predilection for adolescents and young adults 15 to 35 years old, with a female predominance. In general, ASPS grows slowly, with a predilection for the trunk and extremities and rarely in the head and neck region. A literature review found only 11 cases of cheek ASPS that have been reported since 1952. This report describes the case of an unusually rapidly growing mass in the cheek of a 36-year-old woman. The superficial location of the mass led to early detection and treatment.

Primary intraosseous adenoid cystic carcinoma of the jaw: clinical and histopathologic analysis.

PURPOSE: Adenoid cystic carcinoma (ACC), formerly known as cylindroma, is a malignant epithelial neoplasm typically derived from the salivary glands. Of all salivary gland tumors, the incidence of malignant salivary gland tumor has been 15 to 32% in the parotid glands, 70 to 90% in the sublingual glands, and about 50% in the minor salivary glands. Intraosseous ACC of the jaw has rarely been reported and is poorly understood. The aim of the present study was to analyze this tumor clinically and histopathologically to improve the diagnosis, management, and treatment. MATERIALS AND METHODS: We collected the records of 16 patients with intraosseous ACC from 1998 to 2013, who had been treated at our hospital, including clinical data and follow-up information. We then analyzed the patients' clinical features, diagnosis, treatment, and prognosis. RESULTS: The average age of the 16 patients was 56.8 years, and the male/female ratio was 0.8. The primary manifestations of the tumor were obviously different. Tumor excision was performed and followed by radiotherapy or chemotherapy, or both. The average follow-up period was 57.2 months, and the average follow-up period for patients who were alive and tumor free was 52.3 months. The survival rate was 68.8% after treatment. All these results were generally in agreement with those from previous reports. CONCLUSIONS: The differential diagnosis of intraosseous ACC from other common tumors of jaws should be determined by the clinical, radiographic, and histopathologic subtypes. For treatment, surgery is the first choice for patients, and radiotherapy or chemotherapy might improve the prognosis in the postoperative period. In addition, the histopathologic subtypes and biologic processes of ACC are related to patient prognosis.

A prospective study of medial sural artery perforator flap with computed tomographic angiography-aided design in tongue reconstruction.

PURPOSE: To investigate the application of the medial sural artery perforator flap in hemiglossectomy reconstruction and evaluate the value of preoperative computed tomographic angiography (CTA) for perforator location. PATIENTS AND METHODS: Nine patients received medial sural artery perforator flaps for tongue reconstruction from August 2013 to January 2014. Of the 9 patients, 5 were male and 4 were female, with a mean age of 51 years (range 22 to 67). The number, location, and course of the perforators were measured on the CTA preoperatively. RESULTS: Of the 9 medial sural artery perforator flaps, 8 survived and 1 had developed necrosis. Thirteen perforators had been visualized by CTA, and 10 of these were used in the operation. No significant difference was found between the CTA location and the intraoperative findings in the perforators' distribution. The mean diameter of the medial sural artery was 1.0 ± 0.3 mm and of the concomitant vein was 2.0 ± 0.7 mm. The mean pedicle length was 9.7 ± 1.0 cm, with 5.1 ± 1.7 cm of the main trunk and 4.6 ± 2.1 cm of the perforator. The average number of muscular vessel branches was 23.9 ± 6.9, with 12.2 ± 5.1 from the main trunk and 10.1 ± 4.4 from the perforators; 1 (10%) perforator was septocutaneous and 9 (90%) were myocutaneous. CONCLUSIONS: The medial sural artery perforator flap is appropriate for medium-size tongue defect reconstruction, with a long pedicle of matching caliber, adequate tissue volume, and minimal donor site morbidity. CTA is a valuable and necessary method for preoperative assessment of the perforator's location.

Update on the surgical management of temporomandibular joint-centered tendon sheath giant cell tumor with intradural extension: introducing a cost-effective method in using temporal bone for skull base reconstruction in preventing brain hernia.

Tendon sheath giant cell tumor is an idiopathic proliferative and destructive disease of the synovium. It is rare and tends to arise in large joints, for example, knee and ankle, but it can also arise in temporomandibular joints (TMJs). Because of its destructive nature, immediate treatment upon diagnosis is recommended. Radical resection proved to be an excellent choice for superior local control. However, the unfavorable anatomic location of TMJ and infratemporal fossa tumor with intradural extension make such a resection impractical. Hereby, we reported a case of resection of a TMJ tendon sheath giant cell tumor with intradural extension using a transcranial approach. This involves a complex radical resection with subsequent reconstruction. Transposition of temporal bone flap is a novel state-of-the-art technique in reconstructing the middle fossa floor defect by providing a three-dimensional rigid architecture to support the brain. Temporal bone flap is a reliable plug for rigid support in preventing brain hernia and cerebrospinal fluid leak. Despite its complexity, this cost-effective technique is relatively straightforward to learn and is applicable across all socioeconomic groups.

Expression patterns of cancer stem cell markers ALDH1 and CD133 correlate with a high risk of malignant transformation of oral leukoplakia.

Molecular markers for predicting oral cancer development in premalignant oral leukoplakia (OL) are urgently needed. The objective of this study was to examine the expression patterns of cancer stem cell markers ALDH1 and CD133 in samples from patients with OL, and determine their prognostic values for subsequent development of oral cancer. Immunohistochemistry for ALDH1 and CD133 was performed in samples from a cohort of 141 patients with biopsy-proven OL who received a mean follow-up of 5.5 years. Patient clinicopathologic and follow-up data were analyzed. Expression of ALDH1 and CD133 was observed in 54 (38.3%) and 32 (22.7%) of 141 patients with OL, respectively. Kaplan-Meier analysis showed that 48.1% patients with ALDH1-positivity developed oral cancer compared with 12.6% those with ALDH1-negativity (p < 0.001). Meanwhile, 59.4% patients with CD133-positivity developed oral cancer compared with 16.5% those with CD133-negativity (p < 0.001). Multivariate analysis revealed that ALDH1 and CD133 expression was associated with 4.17-fold [95% confidence interval (CI), 1.96-8.90; p < 0.001] and 2.86-fold (95% CI, 1.48-5.55; p = 0.002) increased risk of OL transformation, respectively. Collectively, these data demonstrated for the first time that the expression of ALDH1 and CD133 correlated with malignant transformation in a large series of patients with OL who received a long-term follow-up, which suggests that they may serve as predictors to identify OL with a high risk of oral cancer development.

Low Annexin A1 expression predicts benefit from induction chemotherapy in oral cancer patients with moderate or poor pathologic differentiation grade.

BACKGROUND: The benefit of induction chemotherapy in locally advanced oral squamous cell carcinoma (OSCC) remains to be clearly defined. Induction chemotherapy is likely to be effective for biologically distinct subgroups of patients and biomarker development might lead to identification of the patients whose tumors are to respond to a particular treatment. Annexin A1 may serve as a biomarker for responsiveness to induction chemotherapy. The aim of this study was to investigate Annexin A1 expression in pre-treatment biopsies from a cohort of OSCC patients treated with surgery and post-operative radiotherapy or docetaxel, cisplatin and 5-fluorouracil (TPF) induction chemotherapy followed by surgery and post-operative radiotherapy. Furthermore we sought to assess the utility of Annexin A1 as a prognostic or predictive biomarker. METHODS: Immunohistochemical staining for Annexin A1 was performed in pre-treatment biopsies from 232 of 256 clinical stage III/IVA OSCC patients. Annexin A1 index was estimated as the proportion of tumor cells (low and high, <50% and ≥50% of stained cells, respectively) to Annexin A1 cellular membrane and cytoplasm staining. RESULTS: There was a significant correlation between Annexin A1 expression and pathologic differentiation grade (P=0.015) in OSCC patients. The proportion of patients with low Annexin A1 expression was significantly higher amongst those with moderate/poorly differentiated tumor (78/167) compared to those with well differentiated tumor (18/65). Multivariate Cox model analysis showed clinical stage (P=0.001) and Annexin A1 expression (P=0.038) as independent prognostic risk factors. Furthermore, a low Annexin A1 expression level was predictive of longer disease-free survival (P=0.036, HR=0.620) and locoregional recurrence-free survival (P=0.031, HR=0.607) compared to high Annexin A1 expression. Patients with moderate/poorly differentiated tumor and low Annexin A1 expression benefited from TPF induction chemotherapy as measured by distant metastasis-free survival (P=0.048, HR=0.373) as well as overall survival (P=0.078, HR=0.410). CONCLUSIONS: Annexin A1 can be used as a prognostic biomarker for OSCC. Patients with moderate/poorly differentiated OSCC and low Annexin A1 expression can benefit from the addition of TPF induction chemotherapy to surgery and post-operative radiotherapy. Annexin A1 expression can potentially be used as a predictive biomarker to select OSCC patients with moderate/poorly differentiated tumor who may benefit from TPF induction chemotherapy.