Salivary pepsin as an independent predictor of treatment response for laryngopharyngeal reflux: prospective cohort study with multivariate analysis.

To analyze the predictive value of salivary pepsin for treatment outcomes in laryngopharyngeal reflux (LPR) using multivariate analysis that includes various associated factors. This prospective cohort study was conducted between August 2020 and August 2022. Patients with LPR who had symptoms lasting more than 1 month and a reflux symptom index (RSI) of 14 or higher were enrolled. The participants received a 2-month regimen of proton pump inhibitors (PPIs) treatment and lifestyle modification. Salivary pepsin was checked using fasting saliva before treatment. Salivary pepsin was detected more frequently in the good treatment response group (61.1%), compared to 14.3% in the poor response group. Similarly, patients with higher compliance to lifestyle modifications (> 90%) had a higher chance of a good response (91.7%) compared to those with lower compliance, who had a 53.8% chance of a good response. Other clinical factors have no significant association with treatment response. In multivariate analysis, both pretreatment salivary pepsin and higher compliance with lifestyle modification were found to be independent factors for treatment response (OR 14.457, CI 1.075 ~ 194.37 for both). This study found that positive salivary pepsin and strict lifestyle modification are independent predictors of treatment outcomes in LPR.

Detection of Cancer Recurrence Using Systemic Inflammatory Markers and Machine Learning after Concurrent Chemoradiotherapy for Head and Neck Cancers.

Pretreatment values of the neutrophil-to-lymphocyte ratio (NLR) and the platelet-to-lymphocyte ratio (PLR) are well-established prognosticators in various cancers, including head and neck cancers. However, there are no studies on whether temporal changes in the NLR and PLR values after treatment are related to the development of recurrence. Therefore, in this study, we aimed to develop a deep neural network (DNN) model to discern cancer recurrence from temporal NLR and PLR values during follow-up after concurrent chemoradiotherapy (CCRT) and to evaluate the model's performance compared with conventional machine learning (ML) models. Along with conventional ML models such as logistic regression (LR), random forest (RF), and gradient boosting (GB), the DNN model to discern recurrences was trained using a dataset of 778 consecutive patients with primary head and neck cancers who received CCRT. There were 16 input features used, including 12 laboratory values related to the NLR and the PLR. Along with the original training dataset (N = 778), data were augmented to split the training dataset (N = 900). The model performance was measured using ROC-AUC and PR-AUC values. External validation was performed using a dataset of 173 patients from an unrelated external institution. The ROC-AUC and PR-AUC values of the DNN model were 0.828 ± 0.032 and 0.663 ± 0.069, respectively, in the original training dataset, which were higher than the ROC-AUC and PR-AUC values of the LR, RF, and GB models in the original training dataset. With the recursive feature elimination (RFE) algorithm, five input features were selected. The ROC-AUC and PR-AUC values of the DNN-RFE model were higher than those of the original DNN model (0.883 ± 0.027 and 0.778 ± 0.042, respectively). The ROC-AUC and PR-AUC values of the DNN-RFE model trained with a split dataset were 0.889 ± 0.032 and 0.771 ± 0.044, respectively. In the external validation, the ROC-AUC values of the DNN-RFE model trained with the original dataset and the same model trained with the split dataset were 0.710 and 0.784, respectively. The DNN model with feature selection using the RFE algorithm showed the best performance among the ML models to discern a recurrence after CCRT in patients with head and neck cancers. Data augmentation by splitting training data was helpful for model performance. The performance of the DNN-RFE model was also validated with an external dataset.

Fatty Liver and Risk of Head and Neck Cancer in Type 2 Diabetes Mellitus: A Nationwide Cohort Study.

This study is aimed at investigating the association between NAFLD and the risk of HNC separately based on cancer site using a large population-based cohort of patients with T2DM. The data used in this population-based retrospective cohort study were provided by the Korean National Health Insurance Service. The Cox proportional hazards model was used to estimate multivariable adjusted hazard ratios and 95% CIs for the association of the fatty liver index (FLI) and the risk of HNC. During the mean 6.9 years of follow-up, approximately 25.4% of the study cohort had NAFLD, defined as an FLI ≥60. A total of 3543 HNC cases were identified. Overall, patients with a higher FLI had a significantly higher risk of HNC in the oral cavity, pharynx, and larynx compared with patients with an FLI <30. An association was not observed between salivary gland cancer and FLI. There was no association between obesity and HNC. However, obese patients showed a lower risk of cancer for the oral cavity (p = 0.040), pharynx (p = 0.009), and larynx (p < 0.001) than non-obese patients with the same FLI level. Neither obesity nor smoking affected the association between FLI- and HNC-risk in stratified analyses. In T2DM patients, NAFLD was associated with an increased risk of developing HNC in the oral cavity, pharynx, and larynx, but not in the salivary gland.

Prognostic Significance of the Post-Treatment Neutrophil-to-Lymphocyte Ratio in Pharyngeal Cancers Treated with Concurrent Chemoradiotherapy.

BACKGROUND: Even though the pre-treatment neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are well-established prognosticators in various cancers including head and neck cancers, there have been relatively few studies on the clinical significance of the post-treatment values. This study aimed to investigate the changes in NLR and PLR after concurrent chemoradiotherapy (CCRT) and to evaluate their prognostic significance in pharyngeal cancers. METHODS: This study was retrospectively conducted on 461 consecutive patients with primary pharyngeal cancer who had received definitive CCRT. Blood test results before and after CCRT were obtained, and the pre- and post-treatment NLR and PLR were calculated. Patient prognosis was evaluated based on overall survival (OS) and relapse-free survival (RFS). RESULTS: After CCRT, the NLR increased from 2.01 (interquartile range (IQR), 1.53-2.62) to 2.69 (IQR, 1.93-3.81), and the PLR increased from 118.84 (IQR, 92.61-151.63) to 193.19 (IQR, 146.28-262.46). Along with high pre-treatment NLR and high pre-treatment PLR, high post-treatment NLR was also significantly associated with worse OS and RFS (p = 0.013 and p = 0.026). In addition, patients with a high ΔNLR (i.e., the difference between pre- and post-treatment NLRs) had significantly worse OS and RFS (p = 0.013 and p = 0.026). However, only a high pre-treatment NLR (hazard ratio (HR), 2.19; 95% confidence interval (CI), 1.17-4.08; p = 0.014), age (HR, 2.16; 95% CI, 1.14-4.08; p = 0.018), and stage IV (HR, 2.11; 95% CI, 1.15-3.89; p = 0.017) were independent prognostic factors for OS in the multivariate analysis. CONCLUSIONS: In patients with pharyngeal cancers, following CCRT, the NLR and PLR increased significantly from pre-treatment values. Like the pre-treatment NLR and PLR, a high post-treatment NLR and a significant increase in NLR were also associated with poor prognosis. Further prospective studies are required to prove the independent significance of the post-treatment NLR and PLR.

Duration of Effect and Associated Factors of Injection Laryngoplasty.

OBJECTIVE: Injection laryngoplasty (IL) has become a mainstay in the treatment of unilateral vocal fold paralysis due to technical ease and avoidance of open surgery. The duration of IL effect depends on the injected material and has not been defined clearly. We aimed to define the effective duration of IL and to investigate the associated factors. METHODS: Fifty-nine patients who underwent IL for unilateral vocal fold paralysis were included. IL was performed using a cricothyroid membrane approach under local anesthesia. During follow-up, in cases that developed subjective hoarseness with objective glottic insufficiency, a second IL was performed, and loss of IL effect was recorded. The duration of IL was analyzed using Kaplan-Meier estimates, and the associations between duration of effect and various factors such as postinjection voice therapy, injected material, and cause of paralysis were investigated using log-rank test. RESULTS: Of 59 patients, 20 (33.9 %) received a second IL. The median time interval between the first and second IL was 3.3 months (95% CI, 0.4∼27.8 months). The mean duration of effect after IL was 42.5 months (95% CI, 32.1∼52.9 months), and the rate of persisting effect was 63.4% at 1-year after IL (1-year effect rate) and 59.4% at 2 years after IL. The 1-year effect rate was 80.8% in cases with postinjection voice therapy and 57.8% in those without postinjection voice therapy (P = 0.084). Injected material, DM, HTN, patient age and sex, and cause of paralysis had no effect on the 1-year effect rate. CONCLUSIONS: The mean duration of IL effect was 42.5 months, and the rate of persisting effect was 63.4% at 1-year after IL. There were no significant factors affecting the duration of effect, although the duration tended to be slightly longer in cases with postinjection voice therapy. Further study with a prospective, randomized design is needed.

The diagnostic predictive value of neutrophil-to-lymphocyte ratio in thyroid cancer adjusted for tumor size.

The role of systemic inflammation has not been clearly defined in thyroid cancers. There have been conflicting reports on whether systemic inflammatory markers have predictive value for thyroid cancers. We aimed to evaluate the association between systemic inflammatory markers and clinicopathological factors in thyroid cancers and to assess their predictive value for thyroid cancers in detail. Five hundred thirty-one patients who underwent surgery for thyroid nodules were included. The patient population consisted of 99 individuals (18.6%) with benign thyroid nodules and 432 individuals (81.4%) with thyroid cancers. In 432 patients with thyroid cancers, neutrophil-to-lymphocyte ratio (NLR) was significantly higher in the cases with tumors greater than 2 cm than in those with tumors less than 2 cm. (p = 0.027). NLR and platelet-to-lymphocyte ratio (PLR) were significantly higher in cases with lateral lymph node metastasis (LNM) than in those without LNM (p = 0.007 and 0.090, respectively). The nodule size was significantly higher in benign thyroid nodules than in thyroid cancers (p < 0.001). When the cases were stratified by tumor size, NLR was a significant predictor of thyroid cancers in cases with nodules greater than 2 cm (Exp(B) = 1.85, 95% CI = 1.15-2.97, p = 0.011), but not in those with nodules less than 2 cm. In thyroid cancers, preoperative NLR was associated with pathological prognosticators such as tumor size and lateral lymph node metastasis. When the size difference between thyroid cancers and benign thyroid nodules was adjusted, NLR could be a significant predictor of thyroid cancers.

Impact of Remnant Nodules on Immediate and Long-term Outcomes of Voice Therapy for Vocal Fold Nodules.

OBJECTIVES: In this study, we aimed to assess whether remnant vocal fold nodules (VFN) influence immediate and long-term voice outcomes after voice therapy. STUDY DESIGN: This is a retrospective cohort study evaluating immediate and long-term voice outcomes. METHODS: Twenty-five adult patients with VFN who completed voice therapy were included in this study. Patients were classified into remnant (n = 18) and nonremnant (n = 7) groups according to the presence of remnant nodules immediately after completion of voice therapy. Acoustic and perceptual parameters, as well as voice handicap index (VHI), were compared between groups immediately (immediate outcome) and more than 3 months (long-term outcome) after completion of voice therapy. RESULTS: Immediately after voice therapy, there were no significant differences between groups in grade-roughness-breathiness-asthenia-strain (GRBAS) score, jitter, shimmer, noise-to-harmonics ratio, voice range profile, or s/z ratio. Postvoice therapy VHI scores did not significantly differ between the two groups (9.29 ± 8.94 in the nonremnant group vs. 12.78 ± 9.01 in the remnant group, P = 0.392). The overall GRBAS grade of all patients was maintained at 0 or 1 during long-term follow-up. There was no significant difference between the long-term VHI scores of the remnant group (10.00 ± 8.58) and the nonremnant group (5.67 ± 8.71) (P = 0.306). CONCLUSIONS: Immediately after voice therapy, perceptual scores, acoustic parameters, and VHI scores all significantly improved regardless of presence of remnant nodules. Favorable outcomes of voice therapy were maintained during long-term follow-up regardless of presence of remnant nodules after voice therapy.

The Use of Inhaled N-Acetylcysteine for Laryngopharyngeal Reflux Disease: A Randomized Controlled Trial.

OBJECTIVES: Proton pump inhibitors (PPIs) are the mainstay of the medical treatment for laryngopharyngeal reflux disease (LPRD). However, extraesophageal symptoms of LPRD, such as globus, are often refractory to PPI treatment. Many kinds of adjunctive medications have been attempted to address those refractory cases. We aimed to study whether inhaled N-acetylcysteine (NAC), a mucolytic agent, has additive effects for the treatment of LPRD when used in conjunction with PPIs. METHODS: Patients with reflux symptom index (RSI) greater than 13 and reflux finding scores (RFS) greater than 7 were prospectively enrolled and were randomly assigned to control or study group. Patients were treated with oral rabeprazole in the control group and with oral rabeprazole and inhaled NAC in the study group. Patients were followed once a month for 2 months with questionnaires and stroboscopic examination. At every follow-up, RSI and RFS were checked. The extent of improvements of RSI and RFS were evaluated and compared between two groups. RESULTS: With treatment, the mean RSI changed from 21.0 to 7.6 (P < 0.001) in control group and from 19.7 to 4.5 (P < 0.001) in study group. The mean RFS also changed from 12.9 to 7.1 (P < 0.001) in control group and from 13.5 to 6.9 (P < 0.001) in study group. For both RSI and RFS, the extents of improvement were not significantly different between two groups. In patients whose RSI improved less than nine at the first follow-up (poor early responders), RSI became significantly lower in the study group (4.6 ± 2.0) than in the control group (9.5 ± 4.6) at second follow-up (P = 0.019). In good early responders, however, RSI was not significantly different between the two groups in the second follow-up. CONCLUSIONS: In this study, there were no significant differences in the overall outcome between patients treated with inhaled NAC and PPI and those with PPI alone. Interestingly, some additional therapeutic effect of NAC appeared late for the patients with poor early response. Further studies are required to investigate the underlying mechanism for this.

An increase of CD8+ T cell infiltration following recurrence is a good prognosticator in HNSCC.

Programmed death-ligand 1 (PD-L1) expression and CD8-positive tumor-infiltrating lymphocyte (CD8+ TIL) infiltration are essential biomarkers for immune checkpoint inhibitor therapy. The objective of this study was to compare the expression of those biomarkers between initial and recurrent HNSCCs using paired analysis. Prognostic significance of those immunological changes was also investigated. Forty-two consecutive patients with locally recurrent HNSCCs were included. Immunohistochemical staining of CD8 and PD-L1 was done for both initial and recurrent tumor specimens. The IHC findings were verified with mRNA expression profiling. Also, the prognostic impact was analyzed based on overall survival (OS). Recurrent-to-initial (R/I) ratios of CD8+ TILs and PD-L1 were widely variable. CD8+ TIL density and PD-L1 expression decreased in 59.5% and 69% of patients, respectively (R/I ratio < 1). The R/I ratio of CD8A mRNA was significantly higher in patients with a CD8 R/I ratio > 1 (1.7 ± 1.5 vs. 0.6 ± 0.6, p = 0.042). CD8 R/I ratio (> 1) was a good prognosticator for OS (HR 0.293, 95% CI 0.091-0.945, p = 0.040). CD8+ TIL infiltration and PD-L1 expression changed variably following local recurrence of HNSCC. The increase of CD8+ TILs at recurrence was an excellent independent prognosticator.

Delayed Cerebrospinal Fluid Leakage After Treatment of Skull Base Tumors: Case Series of 9 Patients.

INTRODUCTION: Cerebrospinal fluid (CSF) leaks usually happen in the early postoperative period. However, delayed CSF leak can happen several years after treatment. The purpose of this study was to review the characteristics and clinical course of delayed CSF leak after treating skull base tumors. METHODS: We treated 9 patients with delayed CSF leak (occurring at least 3 months after treatment) between December 2015 and February 2018. Clinical data including initial treatment modality for skull base tumor, time between treatment and CSF rhinorrhea, and the result of endoscopic CSF repair were evaluated by retrospective chart review. RESULTS: Nine patients with delayed CSF leak were evaluated. The mean age was 42.3 ± 5.2 (mean ± SD) years. Six patients with pituitary adenomas, 1 with a Rathke cleft cyst, 1 with a meningioma, and 1 with an osteosarcoma were enrolled. Seven patients (78%) received radiation, and the mean radiation dose was 55.7 ± 2.6 Gy. The median time between the end of treatment for the skull base tumor and CSF rhinorrhea was 137.0 (interquartile range 24-145) months. Seven patients (78%) had meningitis at the time of operation. CSF rhinorrhea was treated with endoscopic reconstruction using a multilayer technique. Meningitis was improved without neurologic sequelae after reconstruction and antibiotic therapy. One patient had recurrence of CSF leak. CONCLUSION: Patients with delayed CSF leak are more likely to have a history of radiation and to present with meningitis at diagnosis. Therefore, CSF rhinorrhea should always be suspected, even several years after treatment, if early symptoms of CSF leak develop in patients with a history of skull base tumor.

Effect of Cinacalcet in Kidney Transplant Patients With Hyperparathyroidism.

OBJECTIVE: In dialysis patients, cinacalcet could be an effective alternative to parathyroidectomy for treating hyperparathyroidism. In the present study, we aimed to determine the characteristics of subjects with persistent hyperparathyroidism who require parathyroidectomy despite the use of cinacalcet. METHODS: Nine kidney transplant patients (7 men, 2 women; mean age 53.2 [SD, 8.9] years) who had tertiary hyperparathyroidism were reviewed in a single center. Pre- and postcinacalcet levels of calcium, phosphorous, intact parathyroid hormone (iPTH), and renal function were analyzed to evaluate the effect of cinacalcet treatment in these patients. The baseline parameters before cinacalcet treatment were compared in patients who did and did not undergo parathyroidectomy. RESULTS: Cinacalcet reduced serum calcium levels in all patients (11.48 [SD, 0.73] mg/dL to 10.20 [0.70] mg/dL; P = .008). Serum phosphorous levels significantly increased from 2.28 (SD, 0.77) mg/dL to 3.02 (SD, 0.65) mg/dL (P = .03). The iPTH levels in 7 patients decreased, while the mean level remained unchanged in total subjects. The iPTH levels increased even with cinacalcet treatment in 2 patients. In 3 patients, serum calcium levels abruptly increased after cinacalcet withdrawal. Five patients who showed persistent hypercalcemia due to hyperparathyroidism underwent parathyroidectomy. These 5 patients had significantly different characteristics compared with 4 patients who did not undergo parathyroidectomy: hypercalcemia (11.92 [SD, 0.68] mg/dL vs 10.93 [SD, 0.26] mg/dL; P = .02), hypophosphatemia (1.74 [SD, 0.36] mg/dL vs 2.95 [SD, 0.58] mg/dL; P = .03), and hyperparathyroidism (252.2 [SD, 131.4] pg/dL vs 101.5 [SD, 18.4] pg/dL; P = .02). CONCLUSION: Cinacalcet reduced hypercalcemia due to hyperparathyroidism in the transplant patients. However, patients who had pre-existing higher iPTH, hypercalcemia, and hypophosphatemia needed parathyroidectomy. Therefore, cinacalcet could be considered an alternative to parathyroidectomy in selected patients.

Prognostic Role of Neutrophil-to-Lymphocyte Ratio in Patients with Human Papillomavirus-Positive Oropharyngeal Cancer.

Objective To investigate the prognostic impact of the neutrophil-to-lymphocyte ratio (NLR) for human papillomavirus-positive oropharyngeal cancer (HPV+ OPC). Study Design Retrospective institutional database analysis. Setting Tertiary referral medical center. Material and Methods In total, 104 patients with HPV+ OPC were enrolled. From the blood laboratory data checked within 4 weeks before initiation of primary treatment, NLR was calculated. The association between clinicopathological characteristics and NLR was analyzed, and the prognostic role was evaluated based on overall survival (OS) and disease-free survival (DFS). Results According to the cutoff value (2.42) for NLR, the patients were classified into the low NLR group (n = 61) or the high NLR group (n = 43). High NLR was associated with a higher rate of advanced T classification ( P = .007) and diabetes mellitus ( P = .01). The proportion of surgery-based treatment was lower in the high NLR group (20.9% vs 42.6%, P = .02). The high NLR group showed a lower 5-year OS rate (85.3% vs 96.3%, P = .09) and a lower 5-year DFS rate (68.1% vs 94.7%, P = .01) than those in the low NLR group. Multivariate analysis showed that advanced N classification was a significant predictor for worse 5-year OS (hazard ratio [HR], 17.40; 95% confidence interval [CI], 2.36-128.29) and that both advanced N classification (HR, 7.78; 95% CI, 2.33-25.93) and high NLR (HR, 4.16; 95% CI, 1.24-13.95) were important prognosticators for worse 5-year DFS. Conclusion Elevated pretreatment NLR was associated with poor DFS in patients with HPV+ OPC.

Lateral lymph node metastasis in papillary thyroid carcinoma: A systematic review and meta-analysis for prevalence, risk factors, and location.

BACKGROUND: Lymph node metastasis (LNM) is frequent in papillary thyroid carcinoma (PTC) and is associated with a poor prognosis. Unlike central LNM (CLNM), there are few studies focusing on LLNM. We aimed to investigate the prevalence and the risk factors for LLNM, with its most prevalent sites. METHODS: We performed a comprehensive literature search using the PubMed and EMBASE databases for relevant studies published prior to November 2016 that examined the risk factors for LLNM. RESULTS: Twenty-three studies, including 18,741 patients, were included. The prevalence of LLNM was 20.9% in all patients. CLNM (pooled OR = 7.84, 95% CI = 6.13-10.02, p < .0001), extrathyroidal extension (pooled OR = 3.22, 95% CI = 2.21-4.70, p < .0001), tumor multifocality (pooled OR = 2.19, 95% CI = 1.67-2.89, p < .0001), male sex (pooled OR = 1.72, 95% CI = 1.50-1.98, p < .0001), upper pole location (pooled OR = 2.96, 95% CI = 1.93-4.53, p < .0001), tumor size ≥1.0 cm (pooled OR = 2.49, 95% CI = 1.71-3.61, p < .0001), lymphovascular invasion (pooled OR = 3.96, 95% CI = 2.61-6.03, p < .0001) and tumor bilaterality (pooled OR = 1.31, 95% CI = 1.12-1.53, p = .0006) were significantly associated with LLNM. Most frequently affected areas were levels III and IV. CONCLUSIONS: The prevalence of LLNM was high although the prognostic impact is unknown. The significant risk factors for LLNM were not much different from known risk factors for CLNM.

Using the nasoseptal flap for reconstruction after endoscopic debridement of radionecrosis in nasopharyngeal carcinoma.

BACKGROUND: Radionecrosis is a complication of nasopharyngeal carcinoma (NPC) that is difficult to treat. Endoscopic debridement is the first-line treatment for radionecrosis. After debridement, however, either bone or the internal carotid artery is exposed and requires mucosal coverage. OBJECTIVES: This study sought to demonstrate the effectiveness of a nasoseptal flap (NSF) after endoscopic debridement of radionecrosis in the reconstruction of nasopharyngeal or skull base defects. METHODS: Nine patients with NPC who underwent navigation-guided endoscopic debridement, followed by NSF reconstruction between April 2013 and July 2016, were included. The patients' clinical features and outcomes were evaluated. RESULTS: All nine patients had headaches, and eight had a foul odor associated with their radionecrosis. One patient underwent three radiotherapy treatments, four had two treatments, and the remaining four had just one treatment. The foul odor disappeared after treatment in all the patients who had been affected. The headache was significantly reduced after treatment in all patients. The NSF detached in two patients. In one patient, NSF failed, and the patient experienced postoperative rupture of the internal carotid artery. In the seven other patients, the NSF successfully covered the resultant defects, despite one intraoperative internal carotid artery rupture. Only two patients required further debridement, whereas the others experienced complete healing after just one surgical procedure. The nasopharyngeal surface was healthy-appearing in eight patients (median follow-up, median 11 months). CONCLUSION: Reconstruction by using NSF after endoscopic debridement for radionecrosis of NPC allowed for faster healing and reduced the need for further debridement.

Efficacy of postoperative neck irradiation for regional control in patients with pN0 oral tongue cancer: Propensity analysis.

BACKGROUND: The purpose of this study was to investigate whether adjuvant radiotherapy (RT) is efficacious for regional control and survival in patients with pN0 oral tongue cancer. METHODS: Clinicopathological features of 166 patients with pN0 oral tongue cancer were compared between those who underwent adjuvant RT to the neck (neck RT-positive) and those who did not (neck RT-negative). Study endpoints were isolated regional recurrence and 3-year regional recurrence-free survival (RRFS). Propensity score matching was also performed. RESULTS: Cox regression analysis did not reveal any significant predictor of isolated regional recurrence, including RT field. Three-year RRFS showed modest improvement in neck RT-positive group compared to neck RT-negative group before (92.2% vs 91.9%) and after propensity analysis (93.8% vs 83.3%), without statistical significance (log-rank P = .85 and .37, respectively). CONCLUSION: Despite more frequent unfavorable factors, the neck RT-positive group had a comparable oncologic outcome to the neck RT-negative group, suggesting that a marginal benefit in regional control might be expected from extending the RT field to the neck for pN0 oral tongue cancer.

Multifocality and bilaterality of papillary thyroid microcarcinoma.

OBJECTIVES: Papillary thyroid carcinomas frequently occur as two or more separate foci within the thyroid gland (18%-87%). However, those multifocal tumors are easy to be undetected by preoperative radiologic evaluations, which lead to remnant disease after initial surgery. We aimed to study the incidence of multifocal papillary thyroid microcarcinomas (PTMCs), diagnostic accuracy of preoperative radiologic evaluation, predictive factors, and the chance of bilateral tumors. METHODS: Two hundred and seventy-seven patients with PTMC were included in this study. All patients underwent total thyroidectomy as an initial treatment. Medical records, pathologic reports, and radiological reports were reviewed for analysis. RESULTS: Multifocal PTMCs were detected in 100 of 277 patients (36.1%). The mean number of tumors in each patient was 1.6±1.1, ranging from 1 to 10. The additional tumor foci were significantly smaller (0.32±0.18 cm) than the primary tumors (0.63±0.22 cm) (P<0.001). There was no significant relationship between primary tumor size and the presence of contralateral tumors. With more tumors detected in one lobe, there was greater chance of contralateral tumors; 18.8% with single tumor focus, 30.2% with 2 tumor foci, and 46.2% with 3 or more tumor foci in one lobe. Sensitivity of preoperative sonography was 42.7% for multifocal tumors and 49.0% for bilateral tumors. With multivariate analysis, nodular hyperplasia was the only significant factor for multifocal tumors. CONCLUSION: In cases of PTMCs, the incidence of multifocal tumors is high. However, additional tumor foci are too small to be diagnosed preoperatively, especially under the recent guidelines on radiologic screening tests for papillary thyroid carcinoma. Multifocal PTMCs have high risk of bilateral tumors, necessitating more extensive surgery or more thorough follow-up.

Inflammatory myofibroblastic tumor involving ear lobule.

We present herein an extremely rare case of an inflammatory myofibroblastic tumor (IMT) of the ear lobule with its management. A 50-year-old woman presented with a wart-like mass between the ear lobule and the facial skin. She had been accidentally lacerated her left ear lobule and visited our clinic. The mass had been incidentally found by the patient 1 year before the trauma and growing slowly without pain. Surgical excision and primary closure was performed. Histopathologic examination demonstrated ill-defined margined nodular proliferation of spindle cells in deep dermis with focal stromal hyalinization and lymphoplasmacytic infiltration compatible with the IMT. The patient showed no evidence of recurrence 6 months after surgery. To our knowledge, this is the first report of an IMT occurred in the external ear. Auricular IMT of our case was not aggressive in clinical nature and treated optimally with surgical excision.

Expression of sodium-iodide symporter and TSH receptor in subclinical metastatic lymph nodes of papillary thyroid microcarcinoma.

BACKGROUND: The clinical significance of the subclinical lymph node (LN) metastasis in clinically node-negative (cN0) papillary thyroid microcarcinoma (PTMC) has been debated. We investigated the expression of sodium-iodide symporter (NIS) and thyroid-stimulating hormone receptor (TSHR) in the subclinical metastatic LNs of PTMC, which are crucial prerequisites for the response to radioactive iodine treatment. METHODS: Among 149 consecutive patients who received total thyroidectomy in conjunction with prophylactic central neck dissection for cN0 PTMC from October 2005 to December 2007, 20 who had single PTMC and subclinical LN metastasis (cN0, pN1, single PTMC) were included. Immunohistochemical staining was performed with anti-human NIS antibody and anti-human TSHR antibody in 20 primary tumors and 52 metastatic LNs. RESULTS: NIS and TSHR expression was detected in 19 (95%) and 18 (90%) of 20 PTMCs, respectively. NIS and TSHR expression were also detected in 50 (96.2%) and 39 (75%) of 52 metastatic LNs, respectively. In 85% of patients, the presence of NIS expression in primary PTMCs was concordant with that in corresponding metastatic LNs. Intensities of NIS and TSHR expression were diverse. In 6 of 12 cases of multiple metastatic LNs, the metastatic LNs showed heterogeneous intensities of NIS expression. CONCLUSIONS: The presence of NIS and TSHR expression was observed with high frequency in both PTMCs and corresponding subclinical metastatic LNs. However, the intensity of NIS and TSHR expression was diverse. Multiple metastatic LNs from single primary tumor focus could have heterogeneous intensity of NIS expression.

Prophylactic central lymph node dissection for clinically node-negative papillary thyroid microcarcinoma: influence on serum thyroglobulin level, recurrence rate, and postoperative complications.

BACKGROUND: In papillary thyroid microcarcinoma (PTMC), regional lymph node metastasis (LNM) is associated with a increased locoregional recurrence rate. Yet, prophylactic central lymph node dissection (CLND) targeting subclinical central LNM continues to be a matter of debate in the treatment of PTMC, which generally carries an excellent prognosis. The aim of our study was to investigate the benefits and risks of prophylactic CLND in patients with clinically node-negative PTMC. METHODS: This study included 232 patients who underwent surgery for clinically node-negative PTMC from 1999 to 2006. Of these 232 patients, 113 underwent only total thyroidectomy (TT) and 119 underwent TT in conjunction with prophylactic bilateral CLND (TT with CLND). We then compared serum thyroglobulin (Tg) levels, recurrence rates, and postoperative complications between the 2 groups (TT only and TT with CLND). RESULTS: The postoperative stimulated serum Tg level was significantly less in the TT with CLND group than in the TT only group (1.07 vs. 2.24 ng/mL, respectively; P = .022). The stimulated Tg levels in the 2 groups became similar, however, after low-dose radioactive iodine treatment (0.44 ng/mL vs. 0.69 ng/mL, respectively; P = 0.341). There was no significant difference in 3-year locoregional control rates after TT with CLND and TT only (98.3% vs. 96.5%, respectively; P = .368). Although the frequency of permanent hypocalcemia was approximately 3 times greater in the TT with CLND group (5.6%) than in the TT only group (1.8%), this finding did not reach statistical significance. CONCLUSION: With prophylactic CLND, the postoperative Tg level can significantly decrease. However, prophylactic CLND is not helpful in decreasing short-term locoregional recurrence in patients with clinically node-negative PTMC. Finally, the risk of permanent hypocalcemia may increase after CLND.

Preoperative BRAF mutation has different predictive values for lymph node metastasis according to tumor size.

OBJECTIVE: To investigate whether BRAF mutation of papillary thyroid carcinoma (PTC) has different predictive values for regional lymph node (LN) metastasis according to tumor size. STUDY DESIGN: Prospective cohort study. Setting. A tertiary hospital. SUBJECTS AND METHODS: From January 2009 to August 2009, the authors prospectively enrolled 102 consecutive patients with unifocal PTC based on the findings of ultrasonography-guided fine-needle aspiration biopsy (FNAB). BRAF mutation was tested on preoperative FNAB specimens. Total thyroidectomy and bilateral central neck dissection (± lateral neck dissection) was performed for all patients. Among 102 patients, 71 who were confirmed to have unifocal PTC by the surgical pathology were finally selected. The 71 patients were classified into 3 groups according to their tumor size: group I, ≤0.5 cm; group II, >0.5 cm and ≤1 cm; and group III, >1 cm. LN metastasis was evaluated in the surgical specimen as a dependent variable. The authors investigated whether BRAF mutation is predictive of LN metastasis in each group. RESULTS: Overall, BRAF mutation was a significant predictor of LN metastasis (P = .045). When patients were classified into 3 groups, frequency of LN metastasis increased with tumor size: 4.8%, 50.0%, and 66.7% (P < .001). However, the frequency of BRAF mutation was not different among 3 groups: 61.9%, 56.3%, and 72.2% (P = .536). BRAF mutation was predictive of LN metastasis only in group II (P = .026). CONCLUSION: BRAF mutation of PTC may have differential predictive values for LN metastasis, according to tumor size.