Correlation of 18F-FDG uptake and thyroid cancer stem cells.

BACKGROUND: 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography (18F-FDG PET) has the potential to detect various types of cancers, including thyroid cancer (TC), at a potentially curable stage. Increased uptake of 18F-FDG was observed in anaplastic and poorly differentiated thyroid cancer cells, and PET-positive tumors are more likely to be resistant to 131I treatment. As cancer stem cells (CSCs) possess a dedifferentiated phenotype and are resistant to many anticancer therapies, we hypothesized that the expression of CSC-related markers is correlated with the ability of tumor cells in TC to uptake FDG. METHODS: The present study cohort included 12 patients with TC, who underwent 18F-FDG PET/CT imaging before surgery. Quantitative polymerase chain reaction (QPCR) and immunohistochemical (IHC) staining were performed to analyze the expression patterns of gene markers related to embryonic stem (ES) cells and CSCs in TC. RESULTS: The mRNA expression levels of CSC- (CD133 and CD44) and ES-related genes (Oct4 and Nanog) were higher in TC tissue than in normal thyroid tissue, whereas the mRNA expression levels of thyroid-specific genes (Tg, TSHR, and TTF1) were higher in normal thyroid tissue than in TC tissue. There was a positive and statistically significant correlation between FDG uptake (SUVmax) of tumor and relative mRNA levels of CD133, CD44, Oct4, and Nanog. The IHC results demonstrated that CD133 and Nanog were expressed in TC tissue but not in normal thyroid tissue, however, CD44 expression was observed in both TC and normal thyroid tissue. Comparisons of the clinicopathological parameters between TC tissues with low and high SUVmax demonstrated significant differences in protein level of CD133 but not in that of Nanog. CONCLUSIONS: The pre-therapeutic tumor SUVmax obtained from 18F-FDG PET/CT may be a potential predictor for evaluating the proportion of CSC population in individual patients with TC.

Sarcopenia results in poor survival rates in oral cavity cancer patients.

OBJECTIVE: This study aimed to determine the impact or survival of low skeletal muscle mass (SMM) among patients with oral squamous cell carcinoma (OSCC) undergoing primary surgery. DESIGN: This study was a retrospective cohort study. SETTING: Oral squamous cell carcinoma patients treated at our referral centre from April 2005 to March 2014 were examined. PARTICIPANTS: The cohort comprised 276 patients with OSCC undergoing primary surgery. MAIN OUTCOME MEASURES: Estimated SMM was measured by calculating the cervical skeletal muscle mass from a CT scan of the head and neck. The 5-year overall survival (OS) and disease-specific survival (DSS) were analysed using a multivariable Cox regression model. RESULTS: There were 276 patients with a male-to-female ratio of 12:1. A low SMM (<47.5 cm2 /m2 ) was associated with worse survival. After adjustment for other factors, the result remained robust for OS (hazard ratio [HR] 1.74, 95% confidence interval [CI] 1.14-2.67) and disease-specific survival (HR 1.67, 95% CI 1.04-2.67). In the subgroup analysis, worse OS and DSS were particularly noted in male patients (HR = 1.90, 95% CI 1.22-2.97; HR = 1.91, 95% CI 1.27-3.19) and in those younger than 60 years of age (HR = 1.91, 95% CI 1.14-3.22; HR = 2.12, 95% CI 1.23-3.64) with low SMM. CONCLUSIONS: Low SMM was a significant independent factor that was associated with lower survival in patients who have oral cavity cancers and are undergoing primary surgery. Preoperative CT scans of the head and neck could be utilised to evaluate SMM, predict treatment outcomes and facilitate nutrition management.

Obliquely-arranged double skin paddles: A novel design to reconstruct extensive head and neck defects with a single fibula or peroneal flap.

OBJECTIVE: To reconstruct extensive head and neck defects usually necessitates double free flaps, which require a time-and-manpower-consuming surgical procedure. We present using a single fibula or peroneal flap with the novel design of obliquely-arranged double skin paddles to reconstruct an extensive head and neck defect. METHODS: From 1998 to 2016, eight patients with the age of 52.25 (35-71) years old had extensive head and neck defects after oral cancer ablation. All of the defects were through and through with the size of 16.25 (12-24) cm × 8.8 (4.5-11) cm. Six of the defects were due to buccal cancer. One was due to tongue cancer, and another one was due to gingiva cancer. All the defects were reconstructed with obliquely-arranged double-paddle free fibula or peroneal flaps. The long axis of the skin paddles was arranged at certain angle (30-45 degrees) to the long axis of lower leg, and the two separate skin paddles were used as the form of island flaps by isolating the cutaneous perforators to create a true chimeric flap. RESULTS: The skin paddle sizes were 14 cm × 3 cm-24 cm × 11 cm and 9.5 cm × 4.5 cm-13 cm × 8 cm. The average length of harvested fibula was 19 (10-30) cm. All of the eight flaps survived without obvious donor site morbidity. One patient had partial skin necrosis over recipient site, requiring surgical debridements and closure. One patient had superficial necrosis over the edge of outer skin paddle, which healed spontaneously. After the follow-up periods of 1 month to 3 year and 8 months, two patients died of sepsis. Six of them could resume soft diet and had no saliva drooling. The remaining two remained nasogastric diet and had saliva drooling. CONCLUSION: With the design of obliquely-arranged double paddles, we may maximize the harvested skin area of lateral lower leg to reconstruct an extensive head and neck defect with a single free flap.

Log margin-to-thickness ratio improves disease-specific survival prediction in oral cancer: A single cancer centre database.

OBJECTIVE: We examined whether dynamic margin criteria margin-to-thickness (MTR) ratio has superior predictive value compared with the resection margin or tumour thickness alone in the survival outcome in oral squamous cell carcinoma (OSCC). DESIGN: This is a retrospective cohort study. SETTING: Oral squamous cell carcinoma patients treated in Kaohsiung Veterans General Hospital Cancer Center between January 2006 and December 2013. PARTICIPANTS: A cohort of 302 patients with OSCC who had undergone surgical management. MAIN OUTCOMES MEASURES: Log MTR was calculated for each patient, and survival data were analysed using a multivariable Cox regression model. Discriminative analysis was performed using chi-square, Akaike information criterion (AIC) and Harrell's C tests. RESULTS: After assessing for discriminative ability, the linear trend of log MTR surpassed those of resection margin and tumour thickness in chi-square, AIC and Harrell's C tests for the advanced pathologic T (pT) category. A multivariate Cox proportional hazard regression model revealed that log MTR <33% was associated with less favourable 5-year disease-specific survival (DSS) (P = 0.006) in the entire oral cancer study cohort. Other significant factors included perineural invasion (P = 0.021), pT category, (P = 0.005), pathologic N category (P < 0.001) and differentiation category (P = 0.022). CONCLUSIONS: Log MTR < 33% may be a predictor of less favourable outcome in the DSS of OSCC. Log MTR outperformed both resection margin and tumour thickness alone in terms of discriminative analysis. Our study could help in presurgical planning for high-risk patients and in aiding the decision-making process for adjuvant treatment.

Factors contributing to surgical site infection in patients with oral cancer undergoing microvascular free flap reconstruction.

PURPOSE: Surgical site infections (SSIs) are associated with considerable medical expenditure. While head and neck free flap reconstruction has gradually become routine management following an ablative oncologic resection, reports on factors contributing to the SSIs are lacking. METHODS: We retrospectively analyzed 173 new patients with oral cancer without any antecedent treatment at a tertiary medical center from 2010 to 2015. We determined incidence rates of SSIs within 30 days postoperatively and identified independent risk factors using multivariate logistic regression analysis. RESULTS: Of 173 patients, 67 (38.7%) had SSIs. Multivariate analysis demonstrated operative time [odds ratio (OR) = 1.199, 95% confidence interval (CI) = 1.036-1.389], mandibulectomy (OR = 2.759; 95% CI = 1.245-6.111), and oro-neck communication (OR = 5.358; 95% CI = 2.150-13.355) as independent predictors for SSIs. CONCLUSIONS: For patients with oral cancer undergoing free tissue reconstruction, mandibulectomy, oro-neck communication, and prolonged operative time were associated with increased incidence of SSIs.

A Novel Application of Double-Paddle Peroneal Chimeric Flap as External Sentinel Monitor in Hypopharyngeal Reconstruction.

OBJECTIVES: Monitoring the viability of buried free flaps in hypopharyngeal reconstruction is difficult. Various methods have been proposed to monitor these buried flaps, but limitations remain. METHOD: We present a method of using double-paddle chimeric peroneal flaps that permanently externalizes a flap skin paddle as a monitoring paddle in hypopharyngeal reconstructions. This study was performed in a medical center in southern Taiwan; between 2013 and 2015, 10 patients underwent double-paddle chimeric peroneal flap reconstruction in advanced stages of hypopharyngeal cancer. We retrospectively reviewed the medical records from these surgeries, searching for either short-term postoperative complications or long-term follow-up morbidity and researched relevant articles for comparisons with other monitoring methods. RESULTS: None of the 10 flaps underwent total loss. The rate of stenosis and that of fistula formation was 10%. The average postoperative hospital stay was 39 days. Six of 10 patients were able to resume at least a soft diet after reconstruction, and none of the patients experienced significant complications. CONCLUSIONS: The peroneal flap is a useful flap because it is thin and pliable, has minimal donor site morbidity in patients without peripheral vascular disease, and has the potential of multiple skin paddles so that one skin paddle can be used for monitoring the buried flap. Using this method, direct clinical monitoring is feasible, and early detection of vascular complications is possible. Furthermore, the drawbacks of using a monitoring paddle produced by a deepithelialized bridge can be avoided.

Double-paddle peroneal flap for extensive lip defect reconstruction.

INTRODUCTION: Today, reconstructive surgeons offer an array of options to reconstruct the lip defects. Herein we present our experience of using free double-paddle peroneal flaps for extensive lip defect reconstruction. PATIENTS AND METHODS: From 1996 to 2014, 16 patients with extensive lip defects after tumor ablation were included. Free double-paddle peroneal flaps were used for reconstructions. In terms of flap design, one skin paddle superiorly placed on the lateral lower leg was used to reconstruct intraoral defects, whereas the other was inferiorly located and was used to reconstruct extraoral defects. A part of the inner skin paddle was everted, and the suture line with the outer skin paddle became the new vermilion border. A portion of the outer skin paddle could be de-epithelized and tucked into the fold of the inner skin paddle, leading to greater fullness of the new lip. RESULTS: Skin paddle sizes were 10-15 cm × 3-13 cm and 4-10.5 cm × 2.5-10.5 cm. Venous thrombosis occurred in one patient but was salvaged, and one flap had superficial necrosis over the outer paddle that was conservatively treated. In the 0.5-33 month follow-up period, all patients were able to close their mouths without obvious drooling. CONCLUSION: Free double-paddle peroneal flap transfer could augment lip definition, deepen the labial vestibule, and provide an acute-angle oral commissure, leading to satisfactory oral competency and improved cosmetic results. Therefore, this technique may be considered a viable option for extensive lip defect reconstruction.

Peroneal Flap for Tongue Reconstruction.

Background For large tongue defects, reconstructive surgeons have devised a variety of feasible options, such as radial forearm free flap and anterolateral thigh (ALT) flap. In our institution, peroneal flap has been the workhorse flap for the soft tissue defect in head and neck reconstruction. We present our experience using peroneal flap in tongue reconstruction. Patients and Methods The study included 47 patients who had undergone tongue reconstructions with peroneal flaps after tumor resection. The size and location of the defect after tumor resection determined whether the peroneal flaps could be harvested as pure septocutaneous flaps to solely reconstruct the neotongue or to carry an additional muscle bulk to fill the adjacent defect. Retrospective chart review was used to look for postoperative complications and to perform functional assessments (which were also performed through telephone inquiry). Results Of the 47 patients, 3 (6%) had flap failure and 1 (2.1%) had partial flap necrosis. The hemiglossectomy group had better results than the total glossectomy group with respect to speech and diet, but neither of these results reached statistical significance (p = 1.0 for speech and p = 0.06 for diet). The results of the subtotal glossectomy group were better than those of the total glossectomy group with respect to diet (p = 0.03). No statistically significant differences were noted among the three groups with respect to cosmetic aspect (p = 0.64). Conclusions Considering its reasonable postoperative complication rates and functional results, peroneal flap can be considered a feasible option for tongue reconstruction.

Management of different kinds of head and neck defects with the submental flap for reconstruction.

Head and neck surgeries often accompany with moderate-sized defects that require time-consuming reconstructions by free flaps. The submental flap is a versatile and time-effective option for reconstruction of orofacial defects providing acceptable cosmetic and functional results without requiring microsurgical techniques. A retrospective case series study of patients who underwent reconstruction with the submental flap between 2009 and 2013 was conducted. There were 36 patients (33 men and 3 women), with a mean age of 56.4 years, enrolled in this study. The primary lesion sites included oral cavity (24 patients), pharynx (8 patients), larynx (2 patients), neck (1 patient) as well as maxillary sinus (1 patient). All flaps were harvested as the myocutaneous flaps. All donor sites were closed primarily without the need of additional surgery. No complete loss of the flap was encountered and two cases developed marginal necrosis of the flap. The submental flap had a reliable pedicle and had minimal donor-site morbidity. It is an excellent flap option for patients with small- to medium-sized defects in head and neck region.

The paracrine effect of cancer-associated fibroblast-induced interleukin-33 regulates the invasiveness of head and neck squamous cell carcinoma.

Head and neck squamous cell carcinoma (HNSCC) is one of the leading causes of cancer-related death worldwide. The prognosis of HNSCC is usually poor because of its propensity for extensive invasion, local recurrence and frequent regional lymph node metastasis, even at initial diagnosis. Carcinoma-associated fibroblasts (CAFs), a major type of tumour-surrounding stromal cell, generate mediators through which they interact with tumours and contribute to cancer progression. The orchestration between CAFs and cancer cells is complex. Despite recent studies demonstrating the paracrine effect of stromal cells in the tumour microenvironment on initiation and progression of cancer cells, the major mediator related to CAFs and its underlying mechanism remain unknown. In the present study, we used organotypic culture to investigate CAFs that promote aggressive behaviour of HNSCC cells. Using microarray analysis, we detected abundant expression of interleukin-33 (IL-33) in CAFs and identified IL-33 as a critical mediator in CAF-induced invasiveness. Counteracting IL-33 activity diminished the aggressive phenotype of cancer cells induced by CAFs. Administration of IL-33 promoted cancer cell migration and invasion through induction of epithelial-to-mesenchymal transdifferentiation and increased IL-33 gene expression in cancer cells. In 40 patients with HNSCC, IL-33 expression in CAFs correlated with IL-33 expression in cancer cells. Most cases with a low invasion pattern grading score (IPGS) showed low or no expression of IL-33, whereas most HNSCC cases with high IPGS displayed over-expression of IL-33 in CAFs and cancer cells. High IL-33 expression associated with poor prognosis in terms of nodal metastasis-free survival. These results indicate that CAFs promote cancer invasiveness via paracrine and autocrine effects on microenvironmental IL-33 signalling, and suggest that IL-33 is a potential prognostic biomarker that could be considered in therapeutic strategies for the treatment of patients with HNSCC.

Bifid mandibular canals and the factors associated with their presence: a medical computed tomography evaluation in a Taiwanese population.

OBJECTIVES: To examine distribution of bifid mandibular canals in a Taiwanese population and to evaluate factors contributing to the phenomenon. MATERIAL AND METHODS: Computed tomographic images from 173 subjects (97 females and 76 males) were obtained using a 64-slice multidetector computerized tomography system, and the presence of bifid mandibular canals, as well as their widths and lengths, was examined. Association of length of bifid canals with possible contributing factors, including gender, age, and side of presentation, as well as size of cross-sectional bony area of mandible along the long axis of mandibular canal, was evaluated. RESULTS: Bifid mandibular canals, with mean values of 10.1 and 0.9 mm in length and width, were found in 53 (30.6%) of 173 patients and 64 (18.5%) of 346 hemi-mandibles. Bifid canals appeared more frequently and tend to penetrate mandible with greater lengths in males if compared with those in females. When males were compared with females and when mandibles with bifid canals were compared with ones without, the former tend to present with larger bony area at corresponding levels of cross-sectional plane than the later, respectively. By regression analysis, significant association was found between length of bifid canals and gender, side of hemi-mandible, and bony area at mid-zone of mandibular canal. CONCLUSIONS: Bifid canals were observed in 30.6% of subjects and 18.5% of hemi-mandibles. Significant association between length of bifid canals and gender, side of hemi-mandible, and cross-sectional bony area of mandible was observed.

An innovative smartphone-based otorhinoendoscope and its application in mobile health and teleotolaryngology.

BACKGROUND: The traditional otorhinoendoscope is widely used in the diagnosis of a variety of ear and nose diseases, but only one doctor can use it at a time. It is also very difficult to share observations from one doctor with another doctor. With advances in electronic health technology, the extended potential application of smartphones to support medical practice or mobile health has grown steadily. OBJECTIVE: The first phase of the study discussed how smartphones may be used for otorhinoscopic imaging and image management via an innovative adaptor. The second phase of the study was to evaluate the diagnostic capability of the smartphone-based otorhinoendoscope, as compared to the traditional otorhinoendoscope, and its application in mobile health and teleotolaryngology. METHODS: We designed a unique adaptor to connect the otorhinoendoscope and smartphone in order to perform smartphone-based otorhinoendoscopy. The main aim was to transform the smartphone into an otorhinoendoscope. We devised a method that would allow us to use the smartphone's camera to capture otorhinoscopic images. Using a freely available Web-based real-time communication application platform and the 3G (or WIFI) network, the smartphone-based otorhinoendoscope could synchronize the smartphone-based otorhinoscopic image with smartphones, tablet PCs, computer notebooks, or personal computers. RESULTS: We investigated the feasibility of telemedicine using a smartphone, tablet PC, and computer notebook. Six types of clinical otorhinoscopic images were acquired via the smartphone-based otorhinoendoscope from six patients, which were examined in this study. Three teleconsultants (doctors A, B, and C) reviewed the six types of clinical otorhinoscopic images and made a telediagnosis. When compared to the face-to-face diagnosis, which was made in-person via a traditional otorhinoendoscope, the three teleconsultants obtained scores of a correct primary telediagnosis 83% (5/6), 100% (6/6), and 100% (6/6) of the time, respectively. When the clinical data were provided, the three teleconsultants obtained a correct secondary telediagnosis score of 100% (6/6), 100% (6/6), and 100% (6/6) of the time, respectively. CONCLUSIONS: The use of previously available technologies in the absence of any additional expensive devices could significantly increase the quality of diagnostics while lowering extraneous costs. Furthermore, this could also increase the connectivity between most isolated family doctors and remote referral centers.

Interleukin-8/CXCR1 Signaling Contributes to the Progression of Pulmonary Adenocarcinoma Resulting in Malignant Pleural Effusion.

Pulmonary adenocarcinoma (PADC) treatment limited efficacy in preventing tumor progression, often resulting in malignant pleural effusion (MPE). MPE is filled with various mediators, especially interleukin-8 (IL-8). However, the role of IL-8 and its signaling mechanism within the fluid microenvironment (FME) implicated in tumor progression warrants further investigation. Primary cultured cells from samples of patients with MPE from PADC, along with a commonly utilized lung cancer cell line, were employed to examine the role of IL-8 and its receptor, CXCR1, through comparative analysis. Our study primarily assessed migration and invasion capabilities, epithelial-mesenchymal transition (EMT), and cancer stem cell (CSC) properties. Additionally, IL-8 levels in MPE fluid versus serum, along with immunohistochemical expression of IL-8/CXCR1 signaling in tumor tissue and cell blocks were analyzed. IL-8/CXCR1 overexpression enhanced EMT and CSC properties. Furthermore, the immunocytochemical examination of 17 cell blocks from patients with PADC and MPE corroborated the significant correlation between upregulated IL-8 and CXCR1 expression and the co-expression of IL-8 and CXCR1 in MPE with distant metastasis. In summary, the IL-8/ CXCR1 axis in FME is pivotal to tumor promotion via paracrine and autocrine signaling. Our study provides a therapeutic avenue for improving the prognosis of PADC patients with MPE.

Multiple-parameter evaluation demonstrates low donor-site morbidity after submental flap harvesting.

PURPOSE: The objective of this study was to implement a scoring system to analyze the authors' experience of donor-site morbidity after harvesting a submental flap for the reconstruction of surgical defects at the head and neck region after oncologic resection. MATERIALS AND METHODS: A retrospective case series study was conducted of patients who underwent reconstruction with a submental flap at the Tri-Service General Hospital (Taipei, Taiwan) from 2008 through 2012. Five parameters representing donor-site morbidity (whistling, smiling, neck extension, beard change, and esthetic outcome) were evaluated with a scoring system developed by a blinded panel of 2 clinicians and the patients. Scores were analyzed and compared between patient subgroups. RESULTS: Twenty-two patients (20 men and 2 women; mean age, 56 yr) underwent reconstruction with a submental flap after head and neck tumor ablation. Primary lesion sites included the oral cavity (13 patients), pharynx (6 patients), larynx (1 patient), neck (1 patient), and sinus (1 patient). The means of all 5 parameters evaluated were higher than 8 on a scale of 0 to 9 (whistling, 8.7; smiling, 8.7; beard change, 8.9; neck extension, 8.2; esthetic outcome, 8.2), showing that submental flap harvesting led to low donor-site morbidity. CONCLUSIONS: Donor-site morbidity after submental flap harvesting was evaluated with a scoring system measuring 5 parameters, namely whistling, smiling, beard change, neck extension, and esthetic outcome. In general, donor-site morbidity was very low. This implemented system and these findings will be helpful in future reconstructive surgical planning and management.

Reconstruction of hypopharyngeal defects with submental flap after laryngopharyngectomy.

The submental flap has rekindled interest in using cervical flaps for reconstruction of head and neck defects. In this article, the authors present their experience of using this flap for hypopharyngeal defects after laryngopharyngectomy. This is a retrospective study of six patients who underwent hypopharyngeal defect reconstruction with submental flap from 2008 to 2011, operated upon by a single surgeon (JC Lee). The flap was used primarily to reconstruct defects after tumor extirpation. The maximum flap size was 12 × 7 cm and the minimum size was 9 × 4 cm (average, 10.5 × 5.3 cm). No flap failures were observed. All the donor site defects were closed primarily. Two patients developed a small pharyngocutaneous fistula that resolved spontaneously. No other complications were observed. After speech reeducation, all achieved a good-quality, understandable artificial voice. All patients were able to eat by mouth without the need for tube feeding. The submental flap is an excellent alternative in the reconstruction of hypopharyngeal defects because of its reliability, versatility, pliability, and relative ease of application. Our initial reports confirm that this kind of reconstruction is feasible and time-saving, and restored a good quality of life.

Comparison of the intraoral and transcervical approach in submandibular gland excision.

The purpose of this study is to evaluate the benefits of the intraoral approach for removal of the submandibular gland (SMG) by comparing it with the usual method of the transcervical approach. Sixteen patients who required SMG resection for benign disorders were divided into two surgical groups who underwent surgery via the intraoral (n = 8) or transcervical (n = 8) approach. The intraoral approach (IOA) consisted of an incision on the floor of mouth from the caruncle of Wharton's duct to the retromolar trigone while the transcervical approach (TCA) consisted of an incision along the natural skin crease overlying the gland. The operation time, hospital stay, complications, and cosmetic appearance were compared between groups. The mean operation time of the IOA group was significantly longer than that of the TCA group, but decreased gradually with surgical experience. The mean hospital stay of the IOA group was significantly shorter than that of the TCA group. Most patients (88 %) of the IOA group experienced sensory defects of the lingual nerve, but these symptoms were temporary. No lasting complications were noted in the IOA group; however, one patient of the TCA group had permanent paralysis of the marginal mandibular branch of the facial nerve. The incision scars were invisible owing to the location on the mouth floor in the IOA group, whereas they were apparent even on the natural skin crease of the neck in the TCA group. In conclusion, the SMG can be removed safely and effectively by IOA with the avoidance of an external scar and of injury to the marginal mandibular nerve. We suggest that the IOA be substituted for the TCA as the primary procedure for removal of the SMG in suitably selected patients.

Artificial Neural Network-Assisted Classification of Hearing Prognosis of Sudden Sensorineural Hearing Loss With Vertigo.

This study aimed to determine the impact on hearing prognosis of the coherent frequency with high magnitude-squared wavelet coherence (MSWC) in video head impulse test (vHIT) among patients with sudden sensorineural hearing loss with vertigo (SSNHLV) undergoing high-dose steroid treatment. This study was a retrospective cohort study. SSNHLV patients treated at our referral center from December 2016 to December 2020 were examined. The cohort comprised 64 patients with SSNHLV undergoing high-dose steroid treatment. MSWC was measured by calculating the wavelet coherence analysis (WCA) at various frequencies from a vHIT. The hearing prognosis were analyzed using a multivariable Cox regression model and convolution neural network (CNN) of WCA. There were 64 patients with a male-to-female ratio of 1:1.67. The greater highest coherent frequency of the posterior semicircular canal (SCC) was associated with the complete recovery (CR) of hearing. After adjustment for other factors, the result remained robust (hazard ratio [HR] 2.11, 95% confidence interval [CI] 1.86-2.35). In the feature extraction with Resnet-50 and proceeding SVM in the horizontal image cropping style, the classification accuracy [STD] for (CR vs. partial + no recovery [PR + NR]), (over-sampling of CR vs. PR + NR), (extensive data extraction of CR vs. PR + NR), and (interpolation of time series of CR vs. PR + NR) were 83.6% [7.4], 92.1% [6.8], 88.9% [7.5], and 91.6% [6.4], respectively. The high coherent frequency of the posterior SCC was a significantly independent factor that was associated with good hearing prognosis in the patients who have SSNHLV. WCA may be provided with comprehensive ability in vestibulo-ocular reflex (VOR) evaluation. CNN could be utilized to classify WCA, predict treatment outcomes, and facilitate vHIT interpretation. Feature extraction in CNN with proceeding SVM and horizontal cropping style of wavelet coherence plot performed better accuracy and offered more stable model for hearing outcomes in patients with SSNHLV than pure CNN classification. Clinical and Translational Impact Statement-High coherent frequency in vHIT results in good hearing outcomes in SSNHLV and facilitates AI classification.

Cytoplasmic CD133 expression is a reliable prognostic indicator of tumor regression after neoadjuvant concurrent chemoradiotherapy in patients with rectal cancer.

BACKGROUND: Despite development in therapeutic strategies, such as neoadjuvant concurrent chemoradiotherapy (CCRT), the prognosis of colorectal cancer remains relatively poor. Cancer stem cells (CSC) with several characteristics can lead to therapeutic resistance. CD133 has been identified as a putative CSC marker in colorectal cancer; however, its functional role still needs elucidation. We verified the role of CD133 with emphasis on expression location and correlated the results of CD133 with clinical outcome in colorectal cancer. METHODS: We used immunohistochemistry to investigate the expression of CD133 in samples from 157 patients with colonic adenocarcinoma and from 76 patients with rectal adenocarcinoma who received neoadjuvant CCRT. We also correlated the expression location of CD133 with the clinicopathological parameters and prognosis. RESULTS: CD133 protein was variably overexpressed in colorectal cancer tissues and was present in three locations: apical and/or endoluminal surfaces, cytoplasm, and lumen. Cytoplasmic CD133 expression level correlated significantly with tumor local recurrence (P = 0.025) and survival of patients with colorectal cancer (P = 0.002), and correlated inversely with tumor regression grading (P = 0.021) after CCRT in patients with rectal cancer. CONCLUSIONS: The expression of CD133 in the cytoplasm is closely associated with local recurrence and patient survival, and may provide a reliable prognostic indicator of tumor regression grading in patients with rectal cancer after CCRT. Cytoplasmic CD133 expression may also help identify the surviving cancer cells in areas with nearly total regression after CCRT.

The chemoadjuvant potential of grape seed procyanidins on p53-related cell death in oral cancer cells.

BACKGROUND: To clarify the efficacy of grape seed procyanidin (GSP) on antiproliferative effects related to p53 functional status of oral squamous cell carcinoma (OSCC) for its chemoadjuvant potential. METHODS: We used GSP to investigate SCC-25 cells with wild-type p53 gene and OEC-M1 cells with mutant p53 gene for the assessment of antiproliferative effects including cell viability, cell cycle, apoptosis, migration and invasion potential, and alterations of associated oncoproteins involved in cellular and molecular events. RESULTS: The findings suggest that GSP on OEC-M1 cells leads to cell cycle arrest by increasing the expression of p21(Cip1) /p27(Kip1) protein without functioning mitochondria-mediated apoptosis, whereas GSP on SCC-25 cells inhibits cell proliferation via both G1-phase arrest and mitochondria-mediated apoptosis in a dose-dependent manner as a result of alterations of Bcl-2. GSP also inhibits the migration and invasion of both cells, which are associated with the suppression of matrix metalloproteinases (MMPs), MMP-2 and MMP-9. CONCLUSION: Antiproliferative effectiveness of GSP is closely associated with the p53 status of OSCC cells. GSP displays chemoadjuvant potential via cell cycle blockage and apoptotic induction. Our findings clearly suggest that GSP may play a role as a novel chemopreventive or therapeutic agent for OSCC.

Role of human papillomavirus infection in carcinogenesis of oral squamous cell carcinoma with evidences of prognostic association.

BACKGROUND: Betel nut chewing, cigarette smoking and alcohol drinking are thought to be major environmental risk factors responsible for the development of oral squamous cell carcinomas. Oncogenic human papillomavirus infections have a well-established association with uterine cervical carcinoma. However, little is known about the exact role of human papillomavirus infections in oral squamous cell carcinomas. This study is designed to elucidate the role of human papillomavirus infections in cancer development and prognosis of oral squamous cell carcinomas. METHODS: Molecular techniques including in situ hybridization and immunohistochemistry of p16(INK4A) and p53 for evidences of human papillomavirus in tissue micro-arrays were investigated. RESULTS: Twenty-four of 65 cases of oral squamous cell carcinomas were found positive for in situ hybridization and 14 were found positive for p16(INK4A). The majority of cases without the evidence of human papillomavirus were related to p53 over-expression. There were statistically significant correlations between the results of human papillomavirus test and size or extent of the tumor (P = 0.003) or the stage of oral squamous cell carcinomas (P = 0.015). Kaplan-Meier plot analysis demonstrated a tendency of longer survival in cases of oral squamous cell carcinomas with the evidence of human papillomavirus or positive p16 (INK4A). CONCLUSIONS: Human papillomavirus infections may play a unique role in oral carcinogenesis. Our data strongly suggest that human papillomavirus-positive oral squamous cell carcinomas comprise a distinct clinical and pathological disease entity that appears related to a better outcome with longer survival and bears a causally associated relationship different from other carcinogenic mechanisms.