Strategy for preventing skin paddle necrosis in mandibular reconstruction with free fibula osteocutaneous flap.

BACKGROUND: Non-thrombotic skin paddle necrosis occasionally occurs during mandibular reconstructions with free fibula osteocutaneous flaps. The number of perforators, size of the skin paddle, and ischemia time of the flap are considered as causes of skin paddle necrosis. The importance of donor side selection has also been highlighted. This study aimed to investigate the leading cause of skin paddle necrosis and the optimal reconstructive procedure. METHODS: A total of 66 patients who underwent mandibular reconstruction using a free fibula osteocutaneous flap were retrospectively analyzed. Skin paddle necrosis, number of cutaneous perforators, size of the skin paddle, and ischemia time of the flap were investigated. An incorrect "laterality" was defined as a skin paddle (septum) covering the reconstruction plate. Donor-site morbidity was recorded. RESULTS: Skin paddle necrosis occurred in 15.2% of patients. An incorrect laterality was associated with a higher incidence of skin paddle necrosis (odds ratio, 22.0; 95% confidence interval, 2.5-195; p = .005). Donor-site morbidity was noted in 18.8% of the patients, without any significant difference in terms of the donor side with and without skin graft (p = .592). The postoperative activities of daily living were not affected. CONCLUSIONS: To prevent skin paddle necrosis, donor side selection is an important safety strategy during mandibular reconstruction with free fibula osteocutaneous flap. The postoperative activities of daily living were found to be little affected by differences in the donor side.

Neutrophil-lymphocyte ratio associated with poor prognosis in oral cancer: a retrospective study.

BACKGROUND: Prognostic biomarkers provide essential information about a patient's overall outcome. However, existing biomarkers are limited in terms of either sample collection, such as requiring tissue specimens, or the process, such as prolonged time for analysis. In view of the need for convenient and non-invasive prognostic biomarkers for oral cancer, we aimed to investigate the prognostic values of neutrophil-to-lymphocyte ratio, lymphocyte-to-monocyte ratio, and platelet-to-lymphocyte ratio in patient survival. We also aimed to explore the associations of these ratios with the clinicopathologic characteristics of Japanese oral squamous cell carcinoma patients. METHODS: This study was a non-randomized retrospective cohort study in a tertiary referral center. We included 433 patients (246 men, 187 women) who underwent radical surgery for oral cancers between January 2001 and December 2013. We evaluated various risk factors for poor prognosis including neutrophil-to-lymphocyte ratio, lymphocyte-to-monocyte ratio, and platelet-to-lymphocyte ratio with univariate and multivariate analyses. The disease-specific survival and overall survival rates of patients were compared among the factors and biomarkers. RESULTS: In multivariable Cox proportional hazards analysis, high neutrophil-to-lymphocyte ratio (hazard ratio 2.87, 95% confidence interval 1.59-5.19, P <  0.001), moderately or poorly differentiated histology (hazard ratio 2.37, 95% confidence interval 1.32-4.25, P <  0.001), and extranodal extension (hazard ratio 1.95, 95% confidence interval 1.13-3.35, P = 0.016) were independent predictors of disease-specific survival. High neutrophil-to-lymphocyte ratio (hazard ratio 2.30, 95% confidence interval 1.42-3.72, P <  0.001), moderately or poorly differentiated (hazard ratio 1.72, 95% confidence interval 1.07-2.76, P = 0.025), and extranodal extension (hazard ratio 1.79, 95% confidence interval 1.13-2.84, P = 0.013) were independent predictors of overall survival. CONCLUSIONS: Neutrophil-to-lymphocyte ratio might be a potential independent prognostic factor in Japanese oral squamous cell carcinoma patients.

Long-Term Effects on Volume Change in Musculocutaneous Flaps after Head and Neck Reconstruction.

OBJECTIVE: Musculocutaneous flap reconstruction surgery is one of the standard procedures following head and neck cancer resection. However, no previous studies have classified flaps in terms of muscle and fat or examined them after long-term follow-up. The purpose of this study was to estimate the fat and muscle volume changes in musculocutaneous flaps during long-term follow-up. METHODS: We conducted a retrospective analysis of 35 patients after musculocutaneous flap reconstruction. The total, fat, and muscle volumes of the musculocutaneous flaps were measured using 3-dimensional images. Changes in flap volumes over time (1 month, 1 year [POY1], and 5 years [POY5] postoperatively) were assessed. Flap persistence was calculated using flap volumes at 1 month after reconstruction for reference. RESULTS: Flap persistence at POY5 was 42.0% in total, 64.1% in fat, and 25.4% in muscle. Muscle persistence was significantly decreased (p < 0.0001). In a multiple regression analysis, decreased body mass index (BMI) of ≥ 5% influenced fat persistence less than muscle persistence at POY1; however, there was no significant difference at POY5. Postoperative radiation therapy was associated with a significant decrease in total flap persistence at POY1 (p = 0.046) and POY5 (p = 0.0097). Muscle persistence significantly decreased at POY5 (p = 0.0108). Age significantly influenced muscle volume at POY1 (p = 0.0072). CONCLUSION: Reconstruction flaps are well-preserved with high fat-to-muscle ratios. Recommendations for weight maintenance are necessary for patients less than 2 years after surgery due to the influence of BMI on fat persistence. Radiation therapy is necessary for some patients based on their disease state. Intensity-modulated radiation therapy can be offered to reduce scattering irradiation to normal tissues.

Does salivary duct repositioning prevent complications after tumor resection or salivary gland surgery?

PURPOSE: Tissue that is resected for the treatment of oral tumors often includes salivary gland ducts. At their institution, the authors conserve and transfer as much of the salivary duct as possible during these procedures to avoid obstructive complications. Differentiating these obstructive complications from a metastatic node can be challenging and can confound subsequent oncologic management. This study compared and examined the effectiveness of salivary duct repositioning in decreasing the incidence of obstructive complications. MATERIALS AND METHODS: Cases of oromandibular disease treated with salivary duct resection at Kobe University Graduate School of Medicine from 2008 to 2013 were retrospectively analyzed. Thirty-two cases (25 patients) of Wharton duct resection and 31 cases (31 patients) of Stensen duct resection were included. The incidence of complications after salivary duct repositioning, duct ligation, and retention of the sublingual gland around the Wharton duct was compared. RESULTS: Wharton ducts were repositioned in 30 cases and ligated in 2 cases. Complications, including oral swelling at the Wharton duct, were observed in 5 cases of repositioning and 2 cases of ligation. Stensen ducts were repositioned in 9 cases and ligated in 22 cases. The only complication reported was a single case of salivary fistula after ligation. CONCLUSIONS: Salivary duct repositioning is performed to prevent blockage of physiologic salivary discharge. Complications were more frequently associated with Wharton ducts than with Stensen ducts because of the unique physiologic and anatomic characteristics of the Wharton duct. Repositioning of the salivary duct is a suitable method for preventing complications associated with the Wharton duct.

Long-term follow-up study of radial forearm free flap reconstruction after hemiglossectomy.

Previous studies on postoperative long-term results in patients who underwent reconstructive free flap transfer following hemiglossectomy had some issues, including the heterogeneity of the patient population and the observation period. The present study aimed to evaluate changes of reconstructed tongues in patients who underwent radial forearm free flap (RFFF) after hemiglossectomy with long-term follow-up. We enrolled 23 patients who underwent RFFF after hemiglossectomy with a postoperative follow-up of 5 years or more. Postoperative status (eating, speech, sensation function) was assessed by concise medical inquiries. Morphological changes of flaps were evaluated by reviewing clinical photographs. Hemiglossectomy involving the base of the tongue was performed in 4 cases (17.4%) and was limited to the mobile tongue in 19 cases (82.6%). The mean follow-up was 85.4 months (range, 60-122 months). All patients experienced gradually improved postoperative status. The most significant improvement was found between 1 and 5 years after surgery (P = 0.007), but not between 1 and 3 years (P = 0.075) or between 3 and 5 years (P = 0.530). In almost all of the flaps, there were few morphological changes throughout the follow-up period. Postoperative status in patients who underwent reconstructive RFFF following hemiglossectomy improved sequentially.

CT Evaluation of Morphology of Transferred Fibula for Implant Placement in Reconstructed Mandible.

BACKGROUND: Dental rehabilitation with osseointegrated implants in reconstructed mandibles remains one of the most challenging procedures for oral and maxillofacial surgeons. Satisfactory outcome requires appropriate assessment of graft morphology. There are few analyses of the morphology of fibulae in reconstructed mandibles, although cadaver studies on fibular shape have been performed. MATERIALS AND METHODS: In this study, we used postoperative computed tomography to retrospectively evaluate the shape, height, and orientation of fibulae transferred after mandibulectomy in 19 patients. RESULTS: The average height of transferred fibulae was 14.3 mm (range, 10.8-20.5 mm). The cross-sectional morphology of transferred fibulae could be classified into 2 types: apex and nonapex. The former type included knife-edged and triangular shapes; the latter included square and circular shapes. CONCLUSION: When implant insertion is planned in a reconstructed mandible, the orientation of the apex of transferred fibula should be evaluated preoperatively to allow for adjustments in implant procedure because the ridge at the apex of the fibula is narrow.

Three-dimensional venous visualization with phase-lag computed tomography angiography for reconstructive microsurgery.

BACKGROUND: Most free flap reconstruction complications involve vascular compromise. Evaluation of vascular anatomy provides considerable information that can potentially minimize these complications. Previous reports have shown that contrast-enhanced computed tomography is effective for understanding three-dimensional arterial anatomy. However, most vascular complications result from venous thromboses, making imaging of venous anatomy highly desirable. METHODS: The phase-lag computed tomography angiography (pl-CTA) technique involves 64-channel (virtually, 128-channel) multidetector CT and is used to acquire arterial images using conventional CTA. Venous images are three-dimensionally reconstructed using a subtraction technique involving combined venous phase and arterial phase images, using a computer workstation. RESULTS: This technique was used to examine 48 patients (12 lower leg reconstructions, 34 head and neck reconstructions, and 2 upper extremity reconstructions) without complications. The pl-CTA technique can be used for three-dimensional visualization of peripheral veins measuring approximately 1 mm in diameter. CONCLUSION: The pl-CTA information was especially helpful for secondary free flap reconstructions in the head and neck region after malignant tumor recurrence. In such cases, radical dissection of the neck was performed as part of the first operation, and many vessels, including veins, were resected and used in the first free-tissue transfer. The pl-CTA images also allowed visualization of varicose changes in the lower leg region and helped us avoid selecting those vessels for anastomosis. Thus, the pl-CTA-derived venous anatomy information was useful for exact evaluations during the planning of free-tissue transfers.

Preoperative MR angiography for free fibula osteocutaneous flap transfer.

INTRODUCTION: Magnetic resonance angiography (MRA) is currently considered the most useful test to evaluate the vascular anatomy of the lower leg prior to free fibula osteocutaneous flap transfer. This study aimed to confirm the validity of preoperative MRA. METHODS: In 19 patients underwent free fibula osteocutaneous flap transfer for maxillary and mandibular reconstruction, the MRA and intraoperative findings and the postoperative complications were retrospectively analyzed. The location and number of distal septocutaneous perforators (dSCPs) that were preoperatively identified and harvested with flaps were documented. RESULTS: Preoperative MRA detected dSCPs with 100% sensitivity. MRA findings also revealed the diversity of vascular structures, such as the tibio-peroneal bifurcation location and the anatomical relationship between the peroneal vessels and the fibula. No patients suffered postoperative ischemic complications in the donor leg. The total flap survival rate was 95 %. CONCLUSIONS: Preoperative MRA effectively excluded large vessel anomalies and peripheral vascular disease, and precisely identified the septocutaneous perforators. Additionally, preoperative MRA contributed to a safer fibular osteotomy by predicting the anatomical relationship between the peroneal vessels and the fibula.

Time to Recurrence Associated With Poor Prognosis in Japanese Oral Squamous Cell Carcinoma Patients.

Purpose: Recurrence in oral squamous cell carcinoma (OSCC) is not rare. Due to lack of studies assessing characteristics of recurrent OSCC, including time to recurrence and outcomes, we sought to investigate its characteristics, time to recurrence, and outcomes in Japanese OSCC patients. Methods: This study was a nonrandomized retrospective cohort study in a tertiary referral centre. It included 208 (117 men and 91 women) patients with recurrent oral cancer who underwent major curative surgery in the Department of Oral and Maxillofacial Surgery at Kobe University Hospital between January 1999 and April 2017. The outcomes were disease-specific survival (DSS) and overall survival (OS). Results: In multivariable Cox proportional hazards analysis, the time to recurrence (hazard ratio [HR] 3.55, 95% confidence interval [CI] 1.69-6.63; P = 0.001), extranodal extension (ENE, HR 2.72, 95% CI 1.51-4.89; P = 0.001), and high T stage (HR 2.00, 95% CI 1.01-3.97; P = 0.046) were independent predictors of DSS. The time to recurrence (HR 3.29, 95% CI 1.82-5.96; P < 0.001) and ENE (HR 2.64, 95% CI 1.52-4.56; P = 0.001) were independent predictors of OS. Conclusion: Time to recurrence, extranodal extension, and higher T stage were independent prognosis predictors in OSCC.

Peripheral facial nerve schwannoma at the inferior mandibular margin: a case report.

Schwannomas commonly occur in the head and neck region as acoustic neuromas. Facial nerve schwannomas are rare and usually occur in the temporal region. A 57-year-old woman presented with a mass at the right mandibular margin. Magnetic resonance imaging revealed a schwannoma located immediately caudal to the mental foramen. We were initially uncertain whether it arose from the trigeminal nerve or the facial nerve. Excision was performed under general anesthesia. The mass was encapsulated and easily detached from the surrounding tissue. The nerve of origin was identified proximal to the tumor. A facial nerve origin was confirmed as the muscles supplied by the marginal mandibular branch of the facial nerve moved on nerve stimulation. Nerve fibers were not found distal to the tumor, possibly because they had been cut during excision. We believe that this is the first report of a schwannoma arising from the peripheral facial nerve.

The prospective evaluation and risk factors of dysphagia after surgery in patients with oral cancer.

BACKGROUND: This prospective study investigated the change of swallowing ability using the Swallowing Ability Scale System (SASS) and swallowing-related quality of life (QOL) by Performance Status Scale for Head and Neck Cancer patients (PSS-H&N). This study also investigated the risk factors for postoperative dysphagia in patients who received reconstructive surgery for oral cancer. SUBJECTS AND METHODS: This study included 64 patients (33 men and 31 women) who underwent radical surgery with neck dissection and reconstructive surgery for oral cancers between July 2014 and February 2018. We evaluated risk factors for poor swallowing ability after treatment, including demographic factors, preoperative factors and perioperative factors, with univariate and multivariate analyses. The change of swallowing ability by the SASS and swallowing-related QOL by PSS-H&N were evaluated prospectively prior to the initiation of surgery within 1 week and at 1 and 3 months after treatment. RESULTS: Advanced T stage (T3, 4) (odds ratio (OR) = 79.71), bilateral neck dissection (OR = 20.66) and the resection of unilateral or bilateral suprahyoid muscles (OR = 17.00) were associated with poor swallowing ability after treatment. The scores for time for food intake and Eating in Public were associated with decrease of QOL in the poor group. CONCLUSIONS: We propose that clinicians consider the risk factors identified in this study and pay close attention to the management of oral cancer patients with reconstructive surgery.

Local Application of Transcutaneous Carbon Dioxide Paste Decreases Inflammation and Accelerates Wound Healing.

INTRODUCTION:  Delayed wound healing after surgery lowers the long-term quality of a patient's life and leads to discomfort and pain. However, treatments for wound healing are often difficult and have not yet been fully established. In this study, we investigated the effect of a special paste that can be administered transdermally and holds a non-gaseous carbon dioxide (CO2) source in its carrier, which can be applied to the head and neck region for wound healing in a rat skin defect model. METHODS: Forty-eight Sprague Dawley rats were randomized into control and CO2 groups. We punched a 6.2-mm wound on the back of each rat. The control rats were left untreated, whereas rats in the CO2 group were treated with the CO2 paste every day after surgery. We evaluated wound healing 3, 7, 14, and 21 days after wounding by analyzing the diameter of the wound, gene expression of inflammatory markers vascular endothelial growth factor (VEGF), transforming growth factor (TGF)-ß, hypoxia-inducible factor (HIF)-1α, interleukin (IL)-1ß, and IL-6 using quantitative real-time polymerase chain reaction, hematoxylin and eosin, and immunohistochemical staining patterns. RESULTS: Rats in the CO2 group showed accelerated wound healing compared to those in the control group. Furthermore, VEGF and TGF-ß were overexpressed, whereas HIF-1α, IL-1ß, and IL-6 were downregulated in the rats treated with CO2. Immunohistochemical analysis also revealed similar patterns of expression. CONCLUSION: Taken together, the CO2 paste promoted wound healing by regulating the hypoxic environment, reducing inflammation, and accelerating angiogenesis.

Induced Pluripotent Stem Cell-related Genes Correlate With Poor Prognoses of Oral Squamous Cell Carcinoma.

BACKGROUND/AIM: We recently investigated the contribution of the iPS-related genes SOX2, OCT4, and Nanog to de-differentiation by assaying for their mRNA levels. Given that mRNA expression does not always correlate with the protein levels, the aim of this study was to retrospectively determine the expression of these four iPS-related factors in human OSCC specimens by immunohistochemistry and examine their association with patient prognosis. MATERIALS AND METHODS: iPS cell-related gene expression in 89 OSCC patients by tissue microarray, and its correlation with clinicopathological factors, differentiation, metastasis, and poor prognoses were investigated. RESULTS: No evidence of statistically significant relationships was found between the expression of iPS cell-related genes and clinicopathological parameters. However, our data indicated that KLF4 expression was associated with survival, and poor tumor differentiation. In addition, high expression of KLF4 was an independent poor prognostic factor (p=0.004) for OSCC patients. CONCLUSION: In preoperative biopsies, higher KLF4 and poor differentiation may be clinically effective predictors for the prognosis of oral cancer.

Effect of size difference between hemiglossectomy and reconstruction flap on oral functions: A retrospective cohort study.

BACKGROUND AND OBJECTIVE: Forearm free flaps are used after hemiglossectomy. However, no investigation has been performed on whether oral functions are better preserved when sizes of the resection and reconstruction flap are exact matches, or whether the size of the resection should be changed. We aimed to retrospectively examine whether size differences between the resection and reconstruction flap affect speech and swallowing functions postoperatively, and to determine whether there are more favorable flap size ratios. METHODS: This is a retrospective cohort study of patients undergoing hemiglossectomy using a forearm free flap between 2006 and 2016 at Kobe University Hospital, Japan. The effect of size difference between the resection and reconstruction flap on maintained oral function was assessed. Speech and swallowing functions were assessed, and their correlation with the ratio of the flap size to that of the resected area was determined. With these data, distribution maps of the relationship between the functional level and reconstructed dimension ratio were prepared. The more suitable reconstructed dimension ratio was examined and evaluated. The Fisher exact test, Kruskal-Wallis test, and Scheffe test were used in statistical analyses. RESULTS: Eighty-eight patients underwent hemiglossectomy using a forearm free flap during a 10-year period. Of these cases, 66 patients were included in this study, while 22 were excluded. The ratio of the area of the reconstruction flap to that of the resection site was 0.59-2.79 (median: 1.61). Sixty patients had flaps greater than the resection area, whereas 6 had smaller flaps. Significant differences were found in speech intelligibility and swallowing function when the reconstructed dimension ratio was categorized as follows: ≤1.3, 1.3-1.8, and ≥1.8. CONCLUSION: Our findings suggest that postoperative deterioration of oral functions after hemiglossectomy could be reduced if reconstruction is performed using a forearm free flap with a surface area 1.3 to 1.8 times greater than that of the resection area.

Ionizing Radiation Enhances Paracellular Permeability Through Alteration of Intercellular Junctions in Cultured Human Lymphatic Endothelial Cells.

BACKGROUND: A problematic complication after radiation therapy is lymphedema. Development of lymphedema is associated with an increase in lymphatic paracellular permeability. The current study investigated the effects of radiation on intercellular junctions and paracellular permeability in cultured human dermal lymphatic endothelial cells (HDLECs). METHODS AND RESULTS: Double immunofluorescence staining with vascular endothelial (VE)-cadherin and actin immediately after X-ray irradiation (5 or 20 Gy) was performed. Morphological changes induced by irradiation were assessed. Cell viability and paracellular permeability after irradiation were also evaluated. Broad junctions in which VE-cadherin was accumulated at cell-cell contacts and almost colocalized with actin were significantly decreased in a dose-dependent manner in confluent and sparse irradiated HDLECs. Irradiation shortened the width of VE-cadherin-positive areas at the cell-cell contacts. Actin filaments did not colocalize with VE-cadherin after 20 Gy irradiation. Although cell viability was not affected by irradiation, paracellular permeability significantly increased in a dose-dependent manner. CONCLUSIONS: A dose of 5 or 20 Gy irradiation in HDLECs does not affect cell viability, but changes VE-cadherin mediated intercellular junctions and actin structure, resulting in an increase of paracellular permeability. Further investigations on the regulatory proteins involved in radiation-induced changes, which were observed in the current study, may contribute to development of lymphedema therapy.

Effect of local application of transcutaneous carbon dioxide on survival of random-pattern skin flaps.

INTRODUCTION: Skin flap procedures are widely used to reconstruct skin and soft tissue defects. Skin flap necrosis is a serious postoperative complication. Many researchers have introduced pharmacological agents to improve flap ischemia in experimental studies. However, outcomes of these studies remain controversial. We previously demonstrated that transcutaneous CO2 application improves hypoxia in fracture repair. In this study, we hypothesized that improving hypoxia by transcutaneous CO2 application can improve the blood flow in skin flaps and increase angiogenesis. We investigated whether transcutaneous CO2 application can increase the survival of random-pattern skin flaps. MATERIALS AND METHODS: Six-week-old male Sprague-Dawley rats were divided into two equal groups: the control group (n = 6) and CO2 group (n = 6). A random-pattern skin flap was constructed in these rats. Topical CO2 was applied using a hydrogel every day for 5 days in the CO2 group. The flap survival area was measured on postoperative days 1, 3, and 5. The vessel density and expression of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and hypoxia-inducible factor-1α (HIF-1α) were evaluated on postoperative day 5. RESULTS: A statistically significant difference was found in the percentage of the flap survival area between the two groups on postoperative days 3 and 5 (p < 0.05). Furthermore, the expression of VEGF and bFGF was significantly higher and that of HIF-1α was significantly lower in the CO2 than in the control group (p < 0.05). CONCLUSIONS: Transcutaneous CO2 application can improve the blood flow in skin flaps and increase angiogenesis, thus increasing the survival of random-pattern skin flaps.

Literature Review of Criteria for Defining Recipient-Site Infection after Oral Oncologic Surgery with Simultaneous Reconstruction.

BACKGROUND: The lack of uniformity of criteria for defining recipient-site infection after oral oncologic surgery with simultaneous reconstruction is problematic despite numerous studies on this issue. This study aimed to investigate the difference in the criteria for defining recipient-site infection after oral oncologic surgery with reconstruction. METHODS: A Medline search was performed via PUBMED using the following combinations of key terms that were tagged in the title, abstract, or both: "surgical site infection-head neck," "surgical site infection-oral cancer," "antibiotic prophylaxis-head neck," and "surgical site infection-oral carcinoma." Search results were filtered between 2005 and 2017. Articles in which there was no mention of the criteria for definition of surgical-site infection were excluded. RESULTS: The number of articles that met the inclusion criteria was 24. The lack of uniformity in the criteria for defining recipient-site infection in each article appeared to be attributable mainly to differences in whether an orocutaneous fistula and superficial incisional infection were regarded as recipient-site infection. CONCLUSION: Reconsideration of the categorization of orocutaneous fistula as infection, regardless of the etiology, and differentiation of superficial and deep incisional infections are necessary for correct assessment of recipient-site infection in oral oncologic surgery.

Single-stage reconstruction for buccal mucosa tumor resection including the labial commissure using a facial artery musculomucosal flap and a vermilion advancement flap.

Resection of buccal mucosa tumors may occasionally involve the labial angle and peripheral skin. Reconstruction is required when the resection involves more than one-third of the lip. We describe a single-stage reconstruction using a facial artery musculomucosal (FAMM) flap and a vermilion advancement flap after buccal mucosa resection including the labial angle. A 62-year-old woman with carcinoma in situ of the buccal mucosa underwent tumor resection. The resection included the right labial angle and peripheral skin. The resection did not lead to a massive lip defect, but a wide defect resulted on the mucosal side. The defect on the mucosal side was reconstructed using a FAMM flap, while the vermilion defect was covered using a vermilion advancement flap. Reconstruction performed using the FAMM flap and vermilion advancement flap produced aesthetically and functionally satisfactory outcomes.

Upregulated Expression of Transient Receptor Potential Cation Channel Subfamily V Receptors in Mucosae of Patients with Oral Squamous Cell Carcinoma and Patients with a History of Alcohol Consumption or Smoking.

OBJECTIVES: Transient receptor potential cation channel (subfamily V, members 1-4) (TRPV1-4) are expressed in skin and neurons and activated by external stimuli in normal mucosae of all oral cavity sites. The oral cavity is exposed to various stimuli, including temperature, mechanical stimuli, chemical substances, and changes in pH, and, notably, the risk factors for oncogenic transformation in oral squamous epithelium are the same as the external stimuli received by TRPV1-4 receptors. Hence, we examined the relationship between oral squamous cell carcinoma (SCC) and TRPV1-4 expression. MATERIALS AND METHODS: Oral SCC patients (n = 37) who underwent surgical resection were included in this study. We investigated the expression of TRPV1-4 by immunohistochemical staining and quantification of TRPV1-4 mRNA in human oral mucosa. In addition, we compared the TRPV1-4 levels in mucosa from patients with SCC to those in normal oral mucosa. RESULTS: The receptors were expressed in oral mucosa at all sites (tongue, buccal mucosa, gingiva, and oral floor) and the expression was stronger in epithelia from patients with SCC than in normal epithelia. Furthermore, alcohol consumption and tobacco use were strongly associated with the occurrence of oral cancer and were found to have a remarkable influence on TRPV1-4 receptor expression in normal oral mucosa. In particular, patients with a history of alcohol consumption demonstrated significantly higher expression levels. CONCLUSION: Various external stimuli may influence the behavior of cancer cells. Overexpression of TRPV1-4 is likely to be a factor in enhanced sensitivity to external stimuli. These findings could contribute to the establishment of novel strategies for cancer therapy or prevention.