Metastasis to hypopharynx from epidermotropic metastatic malignant melanoma.

Previous reports proposed the concept and criteria of epidermotropic metastatic malignant melanoma (EMMM): (a) dermal involvement equal to or broader than the epidermal involvement, (b) atypical melanocytes within the dermis, (c) thinning of the epidermis, (d) widening of the papillary dermis with an epithelial collarette, and (e) vascular invasion of atypical melanocytes. However, it remains unclear whether EMMM also involves the mucosal epithelium. In this case, the patient was diagnosed with EMMM based on the histopathological findings of the patient's multiple skin lesions and clinical course. The patient also developed metastasis to the hypopharynx. Although histopathological findings of the lesion suggested the possibility of melanoma in situ, as the lesion included atypical melanocytes in the mucosal epithelium, the clinical course supported the diagnosis of hypopharyngeal metastasis from EMMM. This case suggests that EMMM may have epitheliotropic features not only in the skin but also in the mucosa.

Significance of Continuous Low-Dose Lenvatinib for the Treating of the Patients with Unresectable Thyroid Carcinoma.

The tyrosine kinase inhibitor lenvatinib has been confirmed as an effective treatment option for patients with unresectable thyroid carcinoma. We conducted a retrospective analysis of the significance of the effect of continued lenvatinib treatment for the longest duration possible at a reasonable daily dose and with a minimum discontinuation period in 42 patients with unresectable thyroid carcinoma treated with lenvatinib between 2015 and 2020. A Cox proportional hazard model-based analysis revealed that the overall survival of the patients treated with a <8 mg/day mean dose of lenvatinib was significantly better than that of the patients treated with 8-24 mg/day (hazard ratio [HR] 0.38 for 1.14-4.54 mg/day, and HR 0.01 for 4.56-7.97 mg/day) adjusted for various factors (e.g., sex, age, drug interruption period). The cumulative dose of lenvatinib administered tended to be higher in the patients treated with low doses (< 8 mg/day) than in the patients treated with relatively high doses (8-24 mg/day). Considering its adverse events, the continuation of lenvatinib treatment with an adequate daily dose and drug interruption may help prolong the survival of patients with unresectable thyroid carcinoma.

A Rare Case of Adult Poorly Differentiated Chordoma of the Skull Base With Rapid Progression and Systemic Metastasis: A Review of the Literature.

Chordoma is a rare tumor that arises from chordal tissue during fetal life. Recently, the concept of poorly differentiated chordoma, a subtype of chordoma characterized by loss of SMARCB1/INI1 with a poorer prognosis than conventional chordomas, was established. It predominantly occurs in children and is rare in adults. Here, we report a rare adult case of poorly differentiated chordoma of the skull base with a unique course that rapidly systemically metastasized and had the shortest survival time of any adult chordoma reported to date. The patient was a 32-year-old male with a chief complaint of diplopia. MRI showed a widespread neoplastic lesion with the clivus as the main locus. Endoscopic extended transsphenoidal tumor resection was performed. Pathological findings showed that the tumor was malignant, and immunohistochemistry revealed a Ki-67 labeling index of 80%, diffusely positive brachyury, and loss of INI1 expression. The final diagnosis was poorly differentiated chordoma. Postoperatively, the residual tumor in the right cavernous sinus showed rapid growth. The patient was promptly treated with gamma knife three fractions. The residual tumor regressed, but the tumor developed systemic metastasis in a short period, and the patient died seven months after diagnosis. This report of a rapidly progressing and fatal adult poorly differentiated chordoma shows the highest Ki-67 labeling index reported to date. Prompt multidisciplinary treatment should be considered when the Ki-67 labeling index is high.

Effect of Aging on Vocal Outcomes After Laryngeal Reinnervation Combined With Arytenoid Adduction.

OBJECTIVE: To evaluate the impact of aging on vocal function following laryngeal reinnervation combined with arytenoid adduction (AA) in the treatment of paralytic dysphonia. METHODS: Sixty-eight patients with unilateral vocal fold paralysis who underwent refined nerve-muscle pedicle flap (NMP) implantation and AA were classified into four groups according to age: under 50 years (-50), in their 50s, 60s, and 70 years and older (70+). These groups consisted of 15, 14, 22, and 17 patients, respectively. Their vocal function was followed periodically for 24 months after surgery. RESULTS: Vocal function in all groups showed significant improvement after surgery. Significant improvements in vocal function were observed during a 24-month follow-up period: maximum phonation time in the -50 and 50 seconds groups; pitch range and voice handicap index-10 in the -50, 50s, and 60s groups; "Grade" in the -50, 50s, and 70+ groups; and "Breathiness" and voice-related quality of life in all groups. There were no significant differences in vocal function among the four groups, except for pitch range, at the 24-month postoperative assessment. CONCLUSIONS: Although the younger groups tended to exhibit better vocal function compared to the older groups 24 months postoperatively, the refined NMP+AA proved effective in the treatment of breathy dysphonia resulting from unilateral vocal fold paralysis, not only in the younger population but also in the older population.

The timing and methods for detection of recurrence in patients with head and neck cancer.

BACKGROUND: Early detection of head and neck cancer recurrence after curative treatment is crucial for effective salvage treatment. OBJECTIVE: We aimed to examine the timing and method that allowed early detection of recurrence in each primary and recurrence site. MATERIALS AND METHODS: We enrolled 440 patients with head and neck squamous cell carcinoma (HNSCC) in the oral cavity, oropharynx, hypopharynx, or larynx who underwent curative treatment focusing on surgery at our hospital between 2009 and 2018. We examined the timing and diagnostic method (clinical examination, patient symptoms, or imaging examination) for HNSCC recurrence according to the primary and recurrence sites. RESULTS: Recurrence was observed in 133 patients. In all primary sites, regional recurrence occurred significantly earlier than local and distant recurrences. Local recurrence occurred later in the larynx than in other primary sites. Furthermore, the clinical examination had a higher ratio of detection of local recurrence in the larynx than in the other primary site. Regardless of the primary site, more than half of the regional recurrences and most of the distant recurrences were detected by imaging examination. CONCLUSIONS AND SIGNIFICANCE: Imaging examination is preferable for achieving early detection of regional and distant recurrences.

Human papillomavirus-related multiphenotypic sinonasal carcinoma: A report of two patients and review of the literature.

Human papillomavirus (HPV)-related multiphenotypic sinonasal carcinoma (HMSC) is a recently described sinonasal tract tumor that is associated with high-risk HPV subtype infection. Despite histological features that are suggestive of a high-grade malignant tumor, the prognosis of HMSC is relatively good; however, the clinical features of this tumor are poorly understood. Here, we describe two patients with HMSC. The first was initially diagnosed with adenoid cystic carcinoma of the right nasal cavity; the tumor was extirpated via endoscopic endonasal surgery. Seventy-four months later, the tumor recurred in the right inferior turbinate and was diagnosed as HMSC after biopsy, whereupon it was resected en block via endoscopic endonasal surgery. No adjuvant therapy was administered during either episode; moreover, no recurrences have occurred during the 44 months since the second operation. The second patient was diagnosed with HMSC based on the biopsy of the tumor occupying the left nasal cavity. The tumor was completely resected under endoscopic endonasal surgery, and no adjuvant therapy was administered. There has been no recurrence for 15 months after the operation. Herein, we also review the clinical features of this tumor type based on 69 previously reported cases as well as our patients.

Efficacy of a new traction method using ring-shaped thread for endoscopic submucosal dissection in the pharynx.

BACKGROUND: Endoscopic submucosal dissection (ESD) is a minimally invasive treatment for pharyngeal cancers. However, pharyngeal ESD is sometimes technically challenging because of the narrow and complex space in which to work. Traction is important to complete the procedure efficiently. Here, we report the technical details and efficacy of a new traction method for pharyngeal ESD using ring-shaped thread and grasping forceps. METHODS: We analyzed pharyngeal ESD performed between January 2016 and March 2021 at our Institute. We designated cases resected using ring-shaped threads "Group R" and those resected without ring-shaped threads as conventional "Group C", and compared the technical outcomes between them. Multivariate analysis and the inverse probability treatment weighting (IPTW) method using propensity scores were adjusted by confounding variables. RESULTS: We analyzed 89 lesions from 68 patients, of which 46 were in Group R and 43 in Group C. Median procedure time and median dissection speed were significantly shorter in Group R than C (37 min vs. 55 min, and 16.0 mm2/min vs. 7.0 mm2/min, respectively, both P < 0.05). These results were confirmed by both multivariate analysis and after IPTW adjustment. All lesions were resected en bloc, and the complete resection rate was not significantly different between Group R and C (91.3% vs. 79.1%, P = 0.14). There were no treatment-related adverse events in either group. CONCLUSIONS: The traction method using ring-shaped thread increases the efficiency of pharyngeal ESD. This simple new traction method should be a useful option for pharyngeal ESD.

Therapeutic outcomes of laryngeal closure and laryngostomy in children with recurrent pneumonia.

PURPOSE: Children with medical complexity frequently experience difficulty breathing and swallowing and occasionally develop aspiration pneumonia. Long-term intubation may cause fatal trachea-innominate artery fistula (TIF). In the present study, we retrospectively evaluated the efficacy of laryngeal closure and laryngostomy in children with medical complexity. MATERIALS AND METHODS: Laryngeal closure and laryngostomy were performed in eight children with severe neuromuscular disorders who were incapable of oral ingestion and verbal communication. The laryngostoma was placed at a higher position compared to that in conventional tracheostomies for easier management of the airway and to prevent TIF. RESULTS: Aspiration was successfully prevented postoperatively in all cases. Laryngocutaneous fistula formation was not observed. Two patients successfully achieved oral ingestion capability and tracheal cannulas were removed in two patients. Among the six patients who needed a mechanical ventilator before surgery, two patients were weaned from mechanical ventilation. Five patients were successfully discharged from the hospital. Although two patients died because of their primary condition, pneumonia exacerbation was not observed in any of the patients. CONCLUSION: Compared to the conventional tracheostomy, our procedure improved airway management and function in children with medical complexity and reduced the risk of TIF.

Clinical impact of gastrointestinal endoscopy on the early detection of pharyngeal squamous cell carcinoma: A retrospective cohort study.

BACKGROUND: In recent years, with the growing availability of image-enhanced gastrointestinal endoscopy, gastroenterologists have contributed to the early detection of pharyngeal squamous cell carcinomas (SCC). AIM: To clarify the clinical characteristics of pharyngeal SCCs detected by gastrointestinal endoscopy. METHODS: This is a retrospective cohort study conducted in a single-center, a university hospital in Japan. We retrospectively assessed the clinical records of 522 consecutive patients with oropharyngeal or hypopharyngeal SCC who were examined in our hospital between 2011 and 2018. The lesions were classified into two groups: Group GE (detected by gastrointestinal endoscopy) and Group non-GE (detected by means other than gastrointestinal endoscopy). The clinical characteristics were compared between the two groups. Continuous data were compared using the Mann-Whitney U test. Pearson's χ 2 test or Fisher's exact test was used to analyze the categorical data and compare proportions. The Kaplan-Meier method was used to estimate the cumulative patient survival rates. RESULTS: In our study group, the median age was 65 years and 474 patients (90.8%) were male. One hundred and ninety-six cases (37.5%) involved the oropharynx and 326 cases (62.5%) involved the hypopharynx. Three hundred and ninety-five cases (75.7%) had some symptoms at the time of diagnosis. One hundred and forty-five (27.8%) cases had concurrent ESCC or a history of ESCC. One hundred and sixty-four (31.4%) cases were detected by gastrointestinal endoscopy and classified as Group GE. The proportions of asymptomatic cases, cTis-1 cases and cases with no lymph node metastasis were significantly higher in Group GE than Group non-GE (61.6% vs 7.3%, P < 0.001, 32.9% vs 12.0%, P < 0.001 and 69.5% vs 19.0%, P < 0.001). Endoscopic laryngo-pharyngeal surgery or endoscopic submucosal dissection were performed in only 0.6% of the lesions in Group non-GE but in 21.3% of the lesions in Group GE (P < 0.001). Overall survival was significantly longer in Group GE than in Group non-GE (P = 0.018). The 2-year and 4-year survival rates were 82.5% and 70.7% in Group GE, and 71.5% and 59.0% in Group non-GE, respectively. CONCLUSION: Gastrointestinal endoscopy plays an important role in the early detection and improving the prognosis of pharyngeal SCCs.

Optimal Management of the Unilateral Recurrent Laryngeal Nerve Involvement in Patients with Thyroid Cancer.

We aimed to determine the optimal management of recurrent laryngeal nerve (RLN) involvement in thyroid cancer. We enrolled 80 patients with unilateral RLN involvement in thyroid cancer between 2000 and 2016. Eleven patients with preoperatively functional vocal folds (VFs) underwent sharp tumor resection to preserve the RLN (shaving group). Thirty-three patients underwent RLN reconstruction with RLN resection (reconstruction group). We divided the reconstruction group into two subgroups based on preoperative VF mobility (normal-reconstruction and paralyzed-reconstruction subgroups). In the cases where RLN reconstruction was difficult, phonosurgeries including arytenoid adduction (AA), with or without thyroplasty type I, or nerve muscle pedicle implantation with AA were performed later (phonosurgery group). We evaluated and compared vocal function among the evaluated periods and different groups. Postoperative vocal function in the shaving and normal-reconstruction subgroups was favorable. There were no significant differences between the two groups. In the paralyzed-reconstruction and phonosurgery groups, postoperative vocal function was significantly improved, and vocal function in the paralyzed-reconstruction subgroup was significantly better than that in the phonosurgery group. For optimal management of unilateral RLN involvement in thyroid cancer, first, sharp dissection should be performed, and if this is impossible, a simultaneous RLN reconstruction procedure should be adopted whenever possible.

Treatment Outcomes of Pulmonary Metastases from Head and Neck Squamous Cell Carcinoma.

Although the lung is the most common site of distant metastases from head and neck squamous cell carcinoma (HNSCC), the number of reports about the effects of pulmonary metastasectomy for the treatment of lung metastasis from HNSCC is limited. Metachronous pulmonary metastases were detected in 45 HNSCC patients at Kumamoto University Hospital from 1998 to 2018. Twenty-two patients underwent an operative resection (Ope group) and 23 underwent chemotherapy (Chemo group). The 3-year overall survival (OS) rate and median OS were evaluated. The effects of adjuvant chemotherapy after pulmonary metastasectomy and of new drugs (cetuximab and nivolumab), in the chemo group were also assessed. The 3-year OS rates and median OS were: Ope, 66.1% and 31.5 months; Chemo, 39.7% and 18 months, respectively. In the Ope group, addi-tional recurrences were significantly fewer in the patients who underwent adjuvant chemotherapy post-surgery versus the patients who underwent surgery alone (p = 0.013). In the Chemo group, the 3-year OS rate of the patients who received new drugs was significantly better than that of the patients who did not (p = 0.021). Adjuvant chemotherapy after pulmonary metastasectomy may be a preferable treatment option for preventing recurrences. Cetuximab and nivolumab have a potential to improve OS.

Swallowing dysfunction following surgery for well-differentiated thyroid cancer with extrathyroid invasion.

BACKGROUND: Differentiated thyroid carcinoma (DTC) can invade the surrounding aerodigestive tract. Radical surgery for locally advanced DTC will require resection of the trachea, recurrent laryngeal nerve (RLN), inferior pharyngeal constrictor muscles (IPCMs), or a part of the esophagus. The purpose of this study was to demonstrate the effect of resection of these surrounding tissues combined with total thyroidectomy and neck dissection on swallowing function following surgery. METHODS: We performed total thyroidectomy combined with neck dissection and resection of the RLN in 24 patients with DTC with extrathyroidal invasion (19 unilateral, 1 bilateral), IPCMs (n = 5), or muscle layers of esophagus (n = 9). Nine patients received a tracheostomy placement due to a window resection of the trachea for tumor invasion (n = 6) and necessary upper airway management (n = 3). We used the duration of nasogastric tube feeding to evaluate swallowing function following surgery. RESULTS: Patients who underwent tracheostomy or IPCM resection showed significantly longer periods of tube feeding (p = 0.0057 and 0.0017, respectively). In contrast, resection of the unilateral RLN or esophageal muscle layer showed no difference in tube feeding duration. Multiple regression analysis indicated that tracheostomy and IPCM resection were significant independent predictors of longer periods of tube feeding (p = 0.04583 and 0.00087, respectively). CONCLUSION: These results indicate that tracheostomy placement and resection of the IPCMs, together with total thyroidectomy, extends the tube feeding duration in the postoperative period.

Effect of pirfenidone injection on ferret vocal fold scars: A preliminary in vivo study.

OBJECTIVES: This study examined the antifibrotic effect of pirfenidone (PFD), which has received regulatory approval in the United States and Japan for treatment of idiopathic pulmonary fibrosis, on the scarred ferret vocal fold (VF) in vivo. METHODS: Eight male ferrets were divided into two groups: saline and PFD. All animals underwent unilateral scarring under anesthesia. The right VF was electrocauterized with ablation of the entire lamina propria. PFD (1.0 mg/mL) or saline injections into right-side scarred VFs were performed (under an operating microscope) 4 weeks later. After an additional 4 weeks, the larynges were harvested for histological analysis. Prior to harvesting, the ferrets were re-anesthetized, and the VFs were observed and recorded using a rigid video laryngoscope. We immunohistochemically evaluated the expression of collagen types I and III, alpha-smooth muscle actin (α-SMA), and fibronectin in the entire lamina propria. We compared the affected areas (calculated using ImageJ software) between the treated (right) and untreated (left) sides within the same animals and between groups. RESULTS: Collagen type I (P = 0.0021) and α-SMA (P = 0.0021) expression levels were lower in the PFD group, but the collagen type III and fibronectin levels did not differ significantly between the two groups. CONCLUSION: PFD injection into the scarred VF is a potentially promising novel antifibrotic treatment. LEVEL OF EVIDENCE: NA Laryngoscope, 130:726-731, 2020.

Detection of hypopharyngeal cancer (Tis, T1 and T2) by ENT physicians vs gastrointestinal endoscopists.

OBJECTIVES: Hypopharyngeal cancer is typically detected at a late stage by ear, nose, and throat (ENT) physicians, when the prognosis is poor. We evaluated how hypopharyngeal cancer (Tis, T1 and T2) were detected by ENT physicians and gastrointestinal endoscopists (GEs) according to the detection reasons. MATERIALS AND METHODS: A total of 109 consecutive patients with hypopharyngeal cancer (Tis, T1 and T2) who received treatment in our institution from January 2014 to February 2018 was enrolled. The detection detail of hypopharyngeal cancer lesions by ENT physicians and GEs, tumor size and location, and the characteristics of the lesions missed by ENT physicians and GEs were reviewed retrospectively. RESULTS: Twenty seven and 82 of 109 (24.8% and 75.2%) patients were detected by ENT physicians and GEs, respectively. The most frequent original reasons for ENT physicians and GEs were both pharyngeal discomfort screening and examination of swollen neck lymph nodes (12 of 27, 44.4% for each) and pre-treatment or follow-up screening for esophageal cancer (25 of 82, 30.5%), respectively. Among the 13 cases of upper gastrointestinal tract screening of the head-and-neck cancer other than pharyngeal cancer detected by GEs, 11 (84.6%) were missed by ENT physicians. In contrast, among the 25 cases of pre-treatment screening of the esophageal cancer detected by GEs, 12 (48%) were missed by other GEs just before the consultation from other institutions. CONCLUSIONS: The percentage of detection of hypopharyngeal cancer (especially, Tis and T1) by ENT physicians is low. A careful examination of the pharynx should be conducted by GEs.

Phonatory function in patients with well-differentiated thyroid carcinoma following meticulous resection of tumors adhering to the recurrent laryngeal nerve.

BACKGROUND: Well-differentiated thyroid carcinomas (WDTCs) sometimes adhere firmly to the recurrent laryngeal nerve (RLN), while allowing normal mobility of the vocal fold (VF). Meticulous dissection of the adhered tumor from the RLN is known to be effective, preserving VF mobility and oncological safety. However, phonatory function following this preservation procedure has yet to be evaluated sufficiently. The objective of this study was to examine phonatory function following the preservation procedure. METHODS: Ten patients with WDTCs, demonstrating normal preoperative VF mobility with tumors adhering to the RLN, underwent the preservation procedure between 2000 and 2013 (preservation group). During the same period, nine patients with WDTCs demonstrating normal VF mobility underwent resection and reconstruction of the tumor-invaded RLNs (reconstruction group). Phonatory function, including maximum phonation time (MPT), mean flow rate (MFR), jitter, shimmer, harmonics-to-noise ratio, and GRBAS scale score, was evaluated and compared statistically between the two groups. RESULTS: The mean values of MPT and MFR in the preservation group were at normal levels. Both G and B scores of GRBAS scale were at near-normal levels. Additionally, the mean B score of the GRBAS scale was significantly better in the preservation group than in the reconstruction group. CONCLUSIONS: When normal VF mobility is observed preoperatively, meticulous resection for preserving RLN would contribute to maintain not only normal level of MPT and MFR, but also to provide better B score of GRBAS scale than RLN resection followed by immediate reconstruction.

Long-term changes in vocal function after supracricoid partial laryngectomy with cricohyoidoepiglottopexy for laryngeal cancer.

BACKGROUND: The purpose of this study was to assess changes in vocal function over time following supracricoid partial laryngectomy with cricohyoidoepiglottopexy (SCL-CHEP). METHODS: A total of 17 patients who underwent SCL-CHEP for laryngeal squamous cell carcinoma between 2007 and 2015 were reviewed. We examined maximum phonation time (MPT), mean airflow rate (MFR), voice intensity, the grade, roughness, breathiness, asthenia, and strain (GRBAS) scale, Voice Handicap Index-10 (VHI-10), and voice-related quality of life (V-RQOL) scores. To assess changes over time in these parameters, we set 3 evaluation periods after surgery: within the first 12 months (term A), 13-36 months (term B), and after 37 months (term C). RESULTS: The mean MPT, MFR, G and B GRBAS subscale, VHI-10, and V-RQOL scores improved significantly over time postoperatively. CONCLUSION: Multiple vocal function parameters improved significantly with time due to self-adaptation to a newly created glottis after surgery.

Delayed transmastoid facial nerve decompression surgery in patients with Ramsay-Hunt syndrome presenting with neurophysiologically complete paralysis.

OBJECTIVES: To determine the efficacy of delayed transmastoid facial nerve decompression in patients with Ramsay Hunt Syndrome (RHS) presenting with complete facial paralysis. METHODS: Twenty-five RHS patients with complete facial nerve paralysis presenting electroneuronographic (ENoG) degeneration ≥90% underwent transmastoid facial nerve decompression more than 3 weeks after the onset of paralysis. The principal features measured were 12 months pre- and post-operative House-Brackmann (HB) grades and the presence of a direct intraoperative neural response (INR) prior to decompression procedure. Correlations between these parameters, and the time between symptom onset and surgery (within or later than 30 and 50 d) were statistically analyzed. RESULTS: Of the 25 patients 13 (52%) exhibited good recovery (HB grade I or II) at 12 months-post-operatively. The timing of decompression generally did not significantly influence outcome but patients treated within 50 d of symptom onset enjoyed better outcomes than those treated later (p = .047). The presence of an INR significantly influenced outcomes (p = .0003). CONCLUSIONS: The success of delayed transmastoid facial nerve decompression in RHS patients was not affected between 25-30 and 30-40 d from symptom onset but was compromised when the delay was >50 d. The presence or absence of an INR was a good predictor of post-operative prognosis.

The Ferret as a Surgical Model for Vocal Fold Scar Creation and Treatment.

OBJECTIVES: To develop a vocal fold (VF) scarring procedure in the ferret, characterize the scars histologically, and test the injectability of the lamina propria (LP). Secondarily, to compare laryngeal anatomy of the ferret with rat and rabbit. MATERIALS AND METHODS: The larynges of 18 male ferrets were prepared by unilateral scarring, and normal larynges from 6 female Wistar rats and 5 male albino rabbits were used for comparative purposes. For scarring, the right VF were electrocauterized, ablating the entire LP. Prior to harvesting the larynges at 4 and 16 weeks, each ferret was re-anesthetized, and in 3 animals, India ink was injected into the LPs of both normal and scarred VFs. RESULTS: Laryngoscopic methods and instrumentation for precise visualization, scarring, and injection were developed. The scarred VFs had reduced hyaluronic acid and increased collagen type I, III, and fibronectin compared with normal VFs. The 2 timepoints (4 and 16 weeks) differed significantly only in collagen type III level (levels were higher at 4 weeks). Injected ink migrated from scarred LP to muscle layer just beneath the scarred tissue 3 hours after injection. CONCLUSION: The ferret is a promising species for creation and experimental treatment of vocal fold scar.

Potential treatment for vocal fold scar with pirfenidone.

OBJECTIVES/HYPOTHESIS: Pirfenidone (PFD) is a strong antifibrotic agent that has been clinically approved in Japan for idiopathic pulmonary fibrosis. We examined the antifibrotic effects of PFD on fibroblasts isolated from scarred vocal folds (VFs) of ferrets in vitro. STUDY DESIGN: Prospective animal experiments with controls. METHODS: Scar fibroblasts (SFs) were isolated from scarred VFs that had been electrocauterized 2 weeks before harvesting (N = 4). Normal fibroblasts (NFs) were isolated from intact VFs (N = 4). SFs and NFs were incubated in the presence of 10 ng/mL transforming growth factor ß1 (TGF-ß1), with or without PFD. After the 48-hour incubation, mRNA expression levels of α smooth muscle actin (αSMA), TGF-ß1, collagen type I, and hyaluronan synthase 2 (HAS2) were examined by real-time polymerase chain reaction. Immunohistochemistry with anti-αSMA anti-collagen type I and phosphorylated Smad (p-Smad)2/3 antibodies in SFs with or without PFD was performed. SFs and NFs were cultured in collagen gel with or without PFD for 48 hours, and the extent of gel contraction was examined quantitatively. RESULTS: PFD treatment significantly (P < .05) decreased mRNA expression of collagen type I, significantly increased mRNA expression of TGF-ß1 and HAS2, and significantly suppressed collagen gel contraction. However, it did not have a significant effect on the expression of αSMA. The expression of p-Smad2/3 in the nucleus was faded with PFD, possibly demonstrating the suppression of translocation of p-Smad2/3 from cytoplasm to nucleus with PFD. CONCLUSIONS: This is the first report to demonstrate the in vitro antifibrotic effects of PFD on fibroblasts isolated from scarred VFs of ferrets. LEVEL OF EVIDENCE: NA. Laryngoscope, 128:E171-E177, 2018.

Laryngeal chondrosarcoma diagnosed by core-needle biopsy.

We report a case of chondrosarcoma of the larynx, diagnosed by a percutaneous core-needle biopsy (CNB). Cartilaginous tumors of the larynx are usually diagnosed by biopsy with direct laryngomicroscopy under general anesthesia. However, patients find it difficult to undergo a biopsy under general anesthesia, for physical, economic, and social reasons. Instead, we can readily detect and sample tumors of the larynx using ultrasound under local anesthesia with reduced stress. Concerning needle-puncture biopsies, including fine-needle aspiration cytology (FNAC) and CNB, some studies have reported needle track dissemination, a possible complication in patients with malignant tumors. Thus, in the head and neck region, we generally use FNAC for biopsies, not CNB. However, it can be difficult to diagnose bone tumors by cytology alone. Regarding primary bone tumors, only one study has reported needle track dissemination by CNB, in osteosarcoma of the femur. Additionally, this complication has not been reported before with chondrosarcoma anywhere in the body. To our knowledge, this is the first report concerning chondrosarcoma of the larynx diagnosed by percutaneous CNB. We recommend CNB as a useful and safe diagnostic technique for primary bone tumors in the head and neck region.