PSMD1 as a prognostic marker and potential target in oropharyngeal cancer.

BACKGROUND: Despite the diverse genetic mutations in head and neck cancer, the chemotherapy outcome for this cancer has not improved for decades. It is urgent to select prognostic factors and therapeutic targets for oropharyngeal cancer to establish precision medicine. Recent studies have identified PSMD1 as a potential prognostic marker in several cancers. We aimed to assess the prognostic significance of PSMD1 expression in oropharyngeal squamous cell carcinoma (OPSCC) patients using immunohistochemistry. METHODS: We studied 64 individuals with OPSCC tissue from surgery at Seoul National University Bundang Hospital between April 2008 and August 2017. Immunostaining analysis was conducted on the tissue microarray (TMA) sections (4 µm) for p16 and PSMD1. H-score, which scale from 0 to 300, was calculated from each nucleus, cytoplasm, and cellular expression. Clinicopathological data were compared with Chi-squared test, Fisher's exact test, t-test, and logistic regression. Survival data until 2021 were achieved from national statistical office of Korea. Kaplan-Meier method and cox-regression model were used for disease-specific survival (DSS) analysis. RESULTS: H-score of 90 in nucleus was appropriate cutoff value for 'High PSMD1 expression' in OPSCC. Tonsil was more frequent location in low PSMD1 group (42/52, 80.8%) than in high PSMD1 group (4/12, 33.3%; P = .002). Early-stage tumor was more frequent in in low PSMD1 group (45/52, 86.5%) than in high PSMD1 group (6/12, 50%; P = .005). HPV was more positive in low PSMD1 group (43/52, 82.7%) than in high PSMD1 group (5/12, 41.7%; P = .016). Patients with PSMD1 high expression showed poorer DSS than in patients with PSMD1 low expression (P = .006 in log rank test). In multivariate analysis, PSMD1 expression, pathologic T staging, and specimen age were found to be associated with DSS (P = .011, P = .025, P = .029, respectively). CONCLUSIONS: In our study, we established PSMD1 as a negative prognostic factor in oropharyngeal squamous cell carcinoma, indicating its potential as a target for targeted therapy and paving the way for future in vitro studies on drug repositioning.

Revisiting Loré's retrograde thyroidectomy from the perspective of preserving the external branch of the superior laryngeal nerve.

Background: Injury to the external branches of the superior laryngeal nerve (EBSLN) is the main reported cause of inexplicable post-thyroidectomy dysphonia (PTD) without recurrent laryngeal nerve (RLN) injury. Loré proposed a retrograde thyroidectomy (RT) technique in which the superior pole is dissected as a final step after the Berry ligament division, making this approach advantageous for protecting the EBSLN. However, evidence of this protective effect remains insufficient. We aimed to evaluate EBSLN function following RT and conventional thyroidectomy (CT) using postoperative electromyography (EMG). Methods: This is a retrospective cohort study conducted at a single tertiary center. Consecutive patients who had undergone CT or RT were included. Bilateral EMG of the cricothyroid muscle was performed 2-3 months postoperatively in all patients. Patient characteristics, postoperative findings of bleeding events, drain amount, hypocalcemia, calcium replacement, RLN function, and EBSLN function were thoroughly reviewed and compared between the two surgical approaches. Abnormalities in the EMG findings were reported based on the wave configuration, and the results were graded into four categories. Results: Seven hundred and thirty-one consecutive patients who underwent CT (n=341), or RT (n=390) were included, and a total of 1,179 RLNs and EBSLNs were at risk in CT (n=601) and RT (n=578). The CT and RT groups had similar clinical characteristics and surgical data. Two groups presented similar postoperative results for bleeding incidence, drain amount, and hypocalcemia. All RLNs were identified in both groups and their permanent function was preserved. EBSLN was significantly less frequently identified in the surgical field during RT than it was during CT (0.3% vs. 4.2%, respectively; P<0.001). Abnormal rates of postoperative EMG on the EBSLN were significantly lower in the RT group than in the CT group (1.7% vs. 7.8%, respectively; P<0.001), while the CT group presented with a higher grade of abnormal EMG (P<0.001). Conclusions: The RT technique may be beneficial for preserving EBSLN function. Meticulous capsular dissection and appropriate traction of the upper pole facilitated by RT are crucial for decreasing the risk of EBSLN injury, which can be achieved without directly identifying the nerve.

Incidence and Clinicopathological Features of Differentiated High-Grade Thyroid Carcinomas: An Institutional Experience.

Differentiated high-grade thyroid carcinoma (DHGTC) is a new entity in the 2022 WHO classification. We aimed to investigate the incidence and clinicopathological features of differentiated HG thyroid carcinoma (DHGTC) and compare the clinicopathological parameters of DHGTC, DTC without HG features, and poorly differentiated thyroid carcinoma (PDTC). A total of 1069 DTCs including papillary thyroid carcinomas (PTCs) and follicular thyroid carcinomas (FTCs) were included in this study. Consecutive 22 PDTCs were also included for comparative purposes. There were a total of 14 (1.3%) cases of DHGTCs, with 13 HGPTCs (1.2% of PTCs) and one HGFTC (6.7% of FTCs). Compared to DTCs without HG features, DHGTCs were associated with larger tumor size, presence of blood vessel invasion, gross extrathyroidal extension, distant metastasis at the time of diagnosis, higher American Joint Committee on Cancer stage, high American Thyroid Association risk, and TERT promoter mutations. DHGTC and PDTC showed a significantly shorter recurrence-free survival (RFS) than DTC without HG features. Multivariate Cox regression analysis revealed that blood vessel invasion, lateral node metastasis, TERT promoter mutations, and HG features were independent prognostic factors (all p < 0.05). When tumor necrosis and increased mitotic count were evaluated separately, tumor necrosis, but not increased mitotic counts, was found to be an independent prognostic factor (p = 0.006). This study confirmed that DHGTC is significantly associated with aggressive clinicopathological features and poor clinical outcomes, similar to PDTC. Although the incidence is low, careful microscopic examination of HG features in DTC is required.

BRAFV600E and TERT promoter C228T mutations on ThyroSeq v3 analysis of delayed skin metastasis from papillary thyroid cancer: a case report and literature review.

BACKGROUND: Skin metastasis from papillary thyroid cancer (PTC) is a rare entity that can occur up to decades after treatment of the primary tumor. Here, we present a patient who developed skin metastasis 10 years after treatment of her primary tumor and describe the molecular findings of the metastatic lesion. CASE PRESENTATION: A 44-year-old female with a history of PTC who underwent a total thyroidectomy and radioactive iodine (RAI) treatment 10 years ago presented with a 1.3-cm skin lesion along the prior thyroidectomy scar. A biopsy revealed metastatic PTC, and the patient underwent surgical excision of the lesion. ThyroSeq molecular testing showed the copresence of BRAFV600E mutation and TERT promoter C228T mutation. The patient subsequently received one round of adjuvant RAI therapy. CONCLUSIONS: A high index of suspicion is warranted in patients with a history of PTC who develop a skin lesion, even several years after remission of the primary disease. In patients with high-risk mutations, such as BRAFV600E and TERT promoter C228T mutations, long-term surveillance of disease recurrence is particularly important.

Cumulative sum analysis of the learning curve for robotic retroauricular thyroidectomy.

Background: Remote-access robotic thyroid surgery enables avoiding a visible scar on the neck and allows precise manipulation through a magnified surgical view. The retroauricular approach has many advantages. This study aimed to evaluate the learning curve for robotic retroauricular thyroidectomy using cumulative sum analysis. Methods: The medical records of 36 patients who underwent robotic retroauricular thyroidectomy between 2018 and 2021 were retrospectively reviewed. The clinical features and surgical outcomes were analyzed; the learning curve was evaluated using the cumulative sum analysis. Results: The learning curve using cumulative sum analysis was divided into two phases based on 15 cases: phase I (first 15 cases) and phase II (remaining 21 cases). The total operation time was significantly shorter in phase II than that in phase I (161.9±23.4 vs. 199±41.0 min, P=0.002). The flap dissection and docking time (77.1±14.3 vs. 90.0±21.5 min, P=0.037) and console time (36.5±16.2 vs. 50.3±17.8 min, P=0.020) were significantly shorter in phase II than that in phase I. There was no significant difference between the two phases in the total amount of drainage, duration of hospital stay, and complications after the surgery. Conclusions: The learning curve for robotic retroauricular thyroidectomy demonstrates that the operation time decreased rapidly after 15 cases. Proficiency in docking and manipulating the instruments accelerate the learning curve.

Early Postoperative Injections of Polydeoxyribonucleotide Prevent Hypertrophic Scarring After Thyroidectomy: A Randomized Controlled Trial.

Objective: Polydeoxyribonucleotide (PDRN) is known to enhance wound healing, but there has been no clinical trial investigating the effect of PDRN on scar prevention in surgical wounds. This study aimed to evaluate the efficacy of PDRN administration in preventing postoperative scars. Approach: In this randomized controlled trial (NCT05149118), 44 patients who underwent open thyroidectomy were randomly assigned to the PDRN treatment or untreated control group. Only patients in the treatment group received two consecutive injections of PDRN 1 and 2 days after surgery. The modified Vancouver Scar Scale (mVSS), patients' subjective symptoms, erythema index (EI), melanin index (MI), and scar height were assessed 3 months after surgery. Results: Patients in the treatment group had lower mVSS scores (1.619 ± 1.244 vs. 2.500 ± 1.540, respectively; p = 0.059) and a significantly lower vascularity subscore (0.476 ± 0.512 vs. 0.900 ± 0.447, respectively; p = 0.010) than those in the control group at the 3-month follow-up. Compared with the control group, the level of subjective symptoms, EI, and scar height were all significantly lowered in the PDRN injection group. No specific side effects related to PDRN injection were observed. Innovation: This is the first clinical study that demonstrated that PDRN injections rapidly decreased postsurgical wound erythema and as a result, significantly reduced both excessive scar formation and accompanying symptoms. Conclusion: Early postoperative injection of PDRN is an effective and safe treatment to prevent hypertrophic scars and improve scar outcomes.

Prolonged persistence of hyaluronic acid after suboptimal vocal fold injection.

Hyaluronic acid (HA) is a commonly used injectable material in temporary vocal fold injections (VFI) in patients with unilateral vocal fold paralysis (UVFP). Hyaluronic acid has generally been known for its three-six months of longevity following VFI. Owing to recent advances in cross-linking technologies, the longevity of HA-based materials, including deep-volumizing cross-linked HA used in VFI, has been improved. However, persisting injectable material in the subepithelial space poses undesirable complications following VFI. Herein, we report 2 cases of unexpected persistence of superficially injected cross-linked HA. In the first case, a 70-year-old man with iatrogenic UVFP received VFI with cross-linked HA three years ago and was referred for persistent dysphonia. Previously injected HA spilled out from the vocal fold (VF) when an epithelial incision was made in the subepithelial cystic lesion. In the second case, a 72-year-old woman with iatrogenic UVFP received VFI with cross-linked HA that migrated into the subepithelial space. Diffuse swelling of the injected VF caused dysphonia that lasted for a year. The previously injected HA spilled out when an epithelial incision was made in the swollen VF. Since superficially injected deep-volumizing cross-linked HA can persist for up to three years, laryngologists should be aware of possible sequelae upon suboptimal VFI with cross-linked HA.

Recurrent Laryngeal Nerve Paralysis Following Thyroidectomy: Analysis of Factors Affecting Nerve Recovery.

OBJECTIVES: Paralysis of the recurrent laryngeal nerves (RLNs), albeit decreased over the years, leaves the surgeon helpless as there is not much that can be done once it occurs. Nimodipine has been suggested as a remedy that could accelerate the recovery of the nerve. Our study aimed to examine the factors that affect the recovery rate (RR) and time to recovery (TTR) of post-thyroidectomy RLN paralysis, with an emphasis on the use of nimodipine. METHODS: A total of 197 patients who had undergone thyroid and parathyroid surgeries were retrospectively reviewed from October 2016 to August 2019. Patients who had RLN paralysis following surgery were assessed. The medical records were retrospectively analyzed to look for possible factors that may influence RLN recovery. RESULTS: A total of 289 nerves were at risk. Temporary RLN paralysis rate was 7.9% while 1.7% was permanent. Age (odds ratio [OR] = 4.8) and intra-operative extra-thyroid extension (OR = 9.0) were independent risk factors for RLN paralysis. The rate of recovery was 82.1%. Loss of signal (LOS; P = .066) was a factor trending for an impact on RR but not nimodipine (P > .05). The mean TTR was 32 days. LOS, nimodipine, and steroid use, among others, were factors trending for an impact on the TTR. CONCLUSION: Although not reaching statistical significance, nimodipine and steroids might influence TTR but not the RR. Larger studies are warranted to address the effect of nimodipine on the outcome of RLN paralysis. LEVEL OF EVIDENCE: 4 Laryngoscope, 132:1692-1696, 2022.

Use of the comprehensive geriatric assessment for the prediction of postoperative complications in elderly patients with head and neck cancer.

BACKGROUND: To determine the efficacy of preoperative Comprehensive Geriatric Assessment (CGA) in predicting postoperative complications in elderly patients undergoing head and neck cancer surgery. METHODS: Medical records of patients aged ≥70 who underwent elective head and neck cancer surgery were reviewed. CGA scores were prospectively collected prior to surgery and analyzed to determine their association with postoperative complications. RESULTS: Of the 65 patients enrolled in this study, 34 (52.3%) with deficits in two or more preoperative CGA domains were categorized as "frail." Fourteen patients (21.5%) experienced postoperative complications. Age was not a risk factor for the complications (p = 0.504). The multivariate analysis indicated that major postoperative complications were significantly associated with frailty (odds ratio [OR] = 21.9, p = 0.039), operation time (OR = 39, p = 0.048), and estimated blood loss (OR = 19.8, p = 0.043). CONCLUSIONS: Frailty assessed by preoperative CGA, but not chronological age, was significantly associated with major postoperative complications in elderly patients undergoing head and neck cancer surgery.

Primary pharyngeal synovial sarcoma in a pediatric patient: A case report.

RATIONALE: Synovial sarcoma is a rare malignant tumor that typically originates from the soft tissue of the extremities. The occurrence of primary pharyngeal synovial sarcoma is even rarer, and few studies have reported its radiological features. Here, we report a case of pediatric primary pharyngeal synovial sarcoma and describe the conventional and advanced magnetic resonance imaging (MRI) findings with pathologic correlation. PATIENT CONCERNS: An 11-year-old girl presented to the otolaryngologic clinic with dysphagia. DIAGNOSIS: Laryngoscopy revealed a large mass in the oropharynx. MRI revealed a well-defined soft tissue mass with a maximal diameter of approximately 5 cm originating from the submucosal space of the oropharynx. The mass was primarily solid and showed homogeneous contrast-enhancement. The mass was hypointense on T1-weighted images and hyperintense on T2-weighted images. The mass showed a homogeneously low apparent diffusion coefficient value on diffusion-weighted imaging, which indicated high tumor cellularity. Dynamic contrast-enhanced MRI revealed a hypovascular tumor with low values of the volume transfer constant between the extracellular extravascular space and blood plasma and blood plasma volume per unit tissue volume. Amide proton transfer-weighted MRI revealed a relatively high amide proton transfer signal in the tumor, indicating a high protein/peptide component. The patient underwent partial surgical resection of the tumor, and the diagnosis of biphasic synovial sarcoma was confirmed on postoperative pathological examination. INTERVENTION: The patient was started on chemotherapy with vincristine, ifosfamide, doxorubicin, and etoposide. OUTCOMES: The tumor did not respond to the 3 cycles of the chemotherapy. Thus, the patient underwent second surgery and subsequent radiation therapy. The patient is now under ifosfamide/carboplatin/etoposide chemotherapy. LESSON: Synovial sarcoma should be considered in the differential diagnosis of pediatric oropharyngeal submucosal tumors. Multimodal MRI may aid diagnosis, although the final diagnosis should be based on the postoperative pathological examination findings.

Intraoperative botulinum toxin injection for superficial partial parotidectomy: A prospective pilot study.

OBJECTIVES: Sialocele and salivary fistula are not serious but troublesome complications after parotidectomy. Various modalities have been introduced to prevent postoperative saliva-related complications. However, clinical trials assessing the prophylactic use of botulinum toxin (BTX) for parotidectomy have not been conducted yet. Herein, we report a pilot study investigating the safety and efficacy of intraoperative BTX (iBTX) injection in partial superficial parotidectomy (PSP). PARTICIPANTS: Patients with benign parotid tumour were prospectively recruited for this clinical trial from 2017 to 2019. The study participants underwent PSP with iBTX injection. We retrospectively reviewed the clinical information of all the consecutive patients who underwent PSP without iBTX from 2013 to 2019. These patients were divided into two groups: the iBTX group (n = 36) and the control group (n = 54). RESULTS: Permanent facial palsy was not observed in either group. Two patients (3.7%) had transient marginal palsy in the control group but none had it in the iBTX group. The incidence of sialocele was significantly lower in the iBTX group than in the control group (2.8% vs. 20.4%, P < .05). Although the incidence of salivary fistula was lower in the iBTX group than in the control group (0% vs. 7.4%), no significant difference was determined between the two groups (P = .147). Total drainage volume was significantly lower in the iBTX group than in the control group (55.0 mL vs. 116.6 mL, P < .001). CONCLUSIONS: iBTX injection may be safe and effective in reducing sialocele and postoperative drainage in PSP. It might be a useful option to prevent saliva-related complications after PSP.

Can the height of the parotid tumor be a predictor of malignancy?

BACKGROUND: Accurate diagnosis of malignancy in the parotid gland before surgery is often challenging. Various clues should be used to increase the index of suspicion for malignancy. We hypothesized that malignant lesions of the parotid gland are located at the superior part of the gland compared to benign ones. METHODS: A total of 169 consecutive patients were included in this study whose medical records were retrospectively reviewed. Benign and malignant tumors were compared in size, height difference from five anatomical landmarks: hard palate, mastoid tip, earlobe, condylar head, and mandibular notch. The cutoff heights from significant landmarks (hard palate, condylar head) were estimated with ROC analysis and chi-square test. RESULTS: Twenty-nine patients (17.2%) were diagnosed with malignant and 140 patients (82.8%) as benign. The height differed significantly between benign and malignant tumors when the reference point was set for the hard palate (P=0.024) and the condylar head (P=0.049), with the cutoff height from reference points to be 22.5, 51.5 mm, respectively. Diagnostic values of parotid level difference presented higher sensitivity (75.9% for hard palate, 72.4% for condylar head vs. 47.8% for fine needle aspiration cytology) and lower false negative rate (24.1% for hard palate, 27.6% for condylar head vs. 52.2% for fine needle aspiration cytology) compared to fine needle aspiration cytology. CONCLUSIONS: Malignant tumors of the parotid gland tend to locate at the superior part of the gland compared to benign tumors. Parotid tumors lying cephalad should raise an index of suspicion for malignancy. Height of the tumor in the parotid gland should be deliberately considered during the first encounter of the patient, which in turn could curate the next step in the diagnostic approach and treatment planning.

A modified V-shaped incision combined with superficial musculo-aponeurotic system flap for parotidectomy.

BACKGROUND: V-shaped incision (VSI) for parotidectomy had been introduced for cosmetic purpose. Despite having aesthetic superiority, it required excessive retraction or an additional hairline incision for adequate surgical exposure. To overcome these problems, we conceptualized a modified VSI approach combined with a separate superficial musculo-aponeurotic system flap. AIMS: This study aimed to propose this approach and evaluate its technical feasibility and efficacy for excision of parotid tumors. MATERIALS AND METHODS: This is a prospective, nonrandomized study involving 74 patients with small-to-medium (<4 cm), benign parotid tumors located superficially. The patients were divided into two groups based on the incision techniques used: modified VSI and modified Blair incision (MBI). The clinical outcomes of both approaches for parotidectomy were analyzed. RESULTS: Thirty-four patients underwent modified VSI approach, while 40 underwent MBI. All parotidectomies with modified VSI were successfully completed without any further incision, and no facial nerve injury or intraoperative tumor rupture complication was reported. There were no significant differences in the complications between both approaches, such as hematoma, infection, wound dehiscence, skin necrosis, sialocele, or sensory disturbance. The modified VSI group showed better cosmetic satisfaction results than did the MBI group (9.2 and 7.8, respectively; p < .001). CONCLUSIONS AND SIGNIFICANCE: The modified VSI approach is safe and feasible for small-to-medium benign parotid tumors. This approach could be a possible option for patients with a high cosmetic demand. LEVEL OF EVIDENCE: 4. STUDY DESIGN: Prospective pilot study.

Preoperative serum VEGF-C but not VEGF-A level is correlated with lateral neck metastasis in papillary thyroid carcinoma.

BACKGROUND: This study aimed to investigate the relationships between serum vascular endothelial growth factor (VEGF)-A or VEGF-C levels and lymph node metastasis (LNM) status in patients with papillary thyroid carcinoma (PTC). METHODS: The study enrolled 150 patients with pathologically proven PTC who underwent surgery: PTC without LNM, PTC with central neck metastasis, and PTC with lateral neck metastasis. RESULTS: Preoperative serum VEGF-A levels were 300.12 ± 80.80 pg/mL overall and were not correlated with the presence of LNM. Preoperative serum VEGF-C levels were 132.41 ± 48.48 pg/mL overall and were significantly correlated with the presence of LNM. Serum VEGF-C levels were further increased in patients with lateral neck metastasis and positively correlated with the number of metastatic LNs (rho = 0.252, P = 0.002). Serum VEGF-C, but not VEGF-A, was identified as a significant predictor of lateral neck metastasis. CONCLUSION: Serum VEGF-C might be a clinically relevant biomarker of lateral neck metastasis in patients with PTC.

Acoustic Characteristics in Epiglottic Cyst.

OBJECTIVE: The purpose of this study was to analyze the acoustic characteristics associated with alternation deformation of the vocal tract due to large epiglottic cyst, and to confirm the relation between the anatomical change and resonant function of the vocal tract. METHODS: Eight men with epiglottic cyst were enrolled in this study. The jitter, shimmer, noise-to-harmonic ratio, and first two formants were analyzed in vowels /a:/, /e:/, /i:/, /o:/, and /u:/. These values were analyzed before and after laryngeal microsurgery. RESULTS: The F1 value of /a:/ was significantly raised after surgery. Significant differences of formant frequencies in other vowels, jitter, shimmer, and noise-to-harmonic ratio were not presented. CONCLUSION: The results of this study could be used to analyze changes in the resonance of vocal tracts due to the epiglottic cysts.

mRNA Expression of SLC5A5 and SLC2A Family Genes in Papillary Thyroid Cancer: An Analysis of The Cancer Genome Atlas.

PURPOSE: The present study investigated the dynamics and prognostic role of messenger RNA (mRNA) expression responsible for ¹8F-fluorodeoxyglucose (FDG) uptake in FDG positron emission tomography (PET) and radioactive iodine (¹³¹I) uptake in whole-body radioactive iodine scans (WBS) in papillary thyroid cancer (PTC) patients. MATERIALS AND METHODS: The primary and processed data were downloaded from the Genomic Data Commons Data Portal. Expression data for sodium/iodide symporter (solute carrier family 5 member 5, SLC5A5), hexokinase (HK1-3), glucose-6-phosphate dehydrogenase (G6PD), and glucose transporter (solute carrier family 2, SLC2A1-4) mRNA were collected. RESULTS: Expression of SLC5A5 mRNA were negatively correlated with SLC2A1 mRNA and positively correlated with SLC2A4 mRNA. In PTC with BRAF mutations, expressions of SLC2A1, SLC2A3, HK2, and HK3 mRNA were higher than those in PTC without BRAF mutations. Expression of SLC5A5, SLC2A4, HK1, and G6PD mRNA was lower in PTC without BRAF mutation. PTCs with higher expression of SLC5A5 mRNA had more favorable disease-free survival, but no association with overall survival. CONCLUSION: Expression of SLC5A5 mRNA was negatively correlated with SLC2A1 mRNA. This finding provides a molecular basis for the management of PTC with negative WBS using ¹8F-FDG PET scans. In addition, higher expression of SLC5A5 mRNA was associated with less PTC recurrence, but not with deaths.

Is cricothyroid muscle twitch predictive of the integrity of the EBSLN in Thyroid Surgery?

OBJECTIVE: Cricothyroid (CT) muscle twitch inspection with neurostimulation is a widely accepted method to identify the external branch of the superior laryngeal nerve (EBSLN) and its integrity in thyroid surgery. However, there has been no large-scale research to evaluate the diagnostic values of CT muscle twitch inspection based on postoperative electromyography (EMG) results, which are considered the gold standard. In this study, we aimed to demonstrate the diagnostic value of CT muscle twitch inspection based on postoperative EMG. STUDY DESIGN: Prospective cohort study. METHODS: A total of 454 patients underwent primary thyroid surgery. Among them, 55 patients were excluded because of preoperative vocal fold palsy, problems with the stimulator, or refusal to participate in the EMG study. Finally, 399 patients were prospectively enrolled in this study. Intraoperatively, CT muscle twitch was inspected with neurostimulation. Bilateral EMG examination of the CT muscle was performed 2 to 3 months postoperatively in all patients. RESULTS: A total of 712 EBSLNs at risk were analyzed in this study. Of these, 21 (2.9%) nerves were visually identified, and positive CT muscle twitch by neurostimulation was observed in 694 (97.5%). Normal results on postoperative EMG of the CT muscle were reported in 657 (92.3%). Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were 97.7%, 5.5%, 92.5%, and 16.7%, respectively. CONCLUSION: CT muscle twitch inspection could be a useful intraoperative tool to determine EBSLN integrity considering its high sensitivity and PPV. However, the test may not completely replace EMG for evaluating EBSLN integrity due to its low specificity and NPV. LEVEL OF EVIDENCE: 2b. Laryngoscope, 2654-2661, 2018.

Gene network inherent in genomic big data improves the accuracy of prognostic prediction for cancer patients.

Accurate prediction of prognosis is critical for therapeutic decisions regarding cancer patients. Many previously developed prognostic scoring systems have limitations in reflecting recent progress in the field of cancer biology such as microarray, next-generation sequencing, and signaling pathways. To develop a new prognostic scoring system for cancer patients, we used mRNA expression and clinical data in various independent breast cancer cohorts (n=1214) from the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) and Gene Expression Omnibus (GEO). A new prognostic score that reflects gene network inherent in genomic big data was calculated using Network-Regularized high-dimensional Cox-regression (Net-score). We compared its discriminatory power with those of two previously used statistical methods: stepwise variable selection via univariate Cox regression (Uni-score) and Cox regression via Elastic net (Enet-score). The Net scoring system showed better discriminatory power in prediction of disease-specific survival (DSS) than other statistical methods (p=0 in METABRIC training cohort, p=0.000331, 4.58e-06 in two METABRIC validation cohorts) when accuracy was examined by log-rank test. Notably, comparison of C-index and AUC values in receiver operating characteristic analysis at 5 years showed fewer differences between training and validation cohorts with the Net scoring system than other statistical methods, suggesting minimal overfitting. The Net-based scoring system also successfully predicted prognosis in various independent GEO cohorts with high discriminatory power. In conclusion, the Net-based scoring system showed better discriminative power than previous statistical methods in prognostic prediction for breast cancer patients. This new system will mark a new era in prognosis prediction for cancer patients.

Some posterior branches of extralaryngeal recurrent laryngeal nerves have motor fibers.

OBJECTIVES/HYPOTHESIS: Anatomical variations of the recurrent laryngeal nerve (RLN), such as extralaryngeal branching, are a well-known risk factor for RLN injury during thyroid surgery. This study aimed to analyze the surgical anatomy and to investigate the existence of posterior branch motor fibers of extralaryngeal RLNs. STUDY DESIGN: Prospective consecutive observational study. METHODS: This was a prospective cohort study of 366 patients between January 2014 and February 2016. Operative data included the type of operation, incidence of nerve bifurcation, the distances among anatomical landmarks. The motor fibers were evaluated using neurostimulation with laryngeal palpation. RESULTS: A total of 667 RLNs at risk were analyzed in this study, and of these 103 (14.5%) nerves were bifurcated or trifurcated before the laryngeal entry point (LEP). More extralaryngeal branched RLNs were observed on the right side than on the left (17.5% vs. 13.3%, P = .294). The mean distance of the LEP point of division was longer on the left side (16.2 ± 6.7 mm) than on the right (14.7 ± 5.9 mm, P = .132). All branched RLNs had a palpable laryngeal twitch when stimulating anterior branches. When stimulating posterior branches, 28.2%(29/103) of branched RLNs showed palpable laryngeal twitch. Overall incidence of posterior motor branch in total RLNs was 4.3% (29/667). CONCLUSIONS: The motor fibers of the RLN are all located in the anterior branch, whereas some posterior branches have motor function. Identification of all of the branches of the RLN may be mandatory to decrease the risk of postoperative nerve injury. LEVEL OF EVIDENCE: 4. Laryngoscope, 127:2678-2685, 2017.