Bilobed Flap for Reconstruction of Skin Defects after Excision of Parotid Carcinoma: A Case Report.

OBJECTIVES: Local flaps, pedicled flaps, and free flaps are used to reconstruct medium-sized skin defects after excision of parotid carcinoma. The bilobed flap is a local flap primarily used by plastic surgeons for small defects of nasal skin. We report a case of parotid carcinoma with skin infiltration successfully treated by skin reconstruction with a bilobed flap. METHODS: An 84-year-old man presented with a parotid mass he had noticed 2 months earlier. Parotid carcinoma with skin infiltration was diagnosed and he underwent radical surgery. The skin defect was round (diameter, 6 cm) and was resected and reconstructed with a bilobed flap designed to be caudal to the defect. RESULTS: Postoperative facial nerve palsy improved within 6 months. The postoperative course was otherwise uneventful, and the patient was discharged on postoperative day 7. Pathological examination revealed a sarcomatoid salivary duct carcinoma. CONCLUSIONS: Bilobed flaps are useful for reconstructing skin defects with a diameter of 6 cm or less.

A Case of Metastatic Submandibular Salivary Duct Carcinoma that Completely Responded to Pembrolizumab Monotherapy.

Salivary gland carcinoma is a rare cancer and has more than 20 histopathological types. Although chemotherapy has been the mainstay of treatment for unresectable carcinomas such as multiple recurrence and distant metastasis, no standard regimen is available. In this article, we report a case of poorly differentiated salivary duct carcinoma of the submandibular gland with distant metastases that was successfully treated with pembrolizumab monotherapy. A 66-year-old man became aware of a left submandibular mass 2 months before his first visit to our department. A needle biopsy at a previous hospital revealed carcinoma, not otherwise specified. The combined positive score on a programmed death ligand-1 immunohistochemistry test was 1-10%. The patient was referred to our department for further treatment. Computed tomography revealed left level II and IV neck lymphadenopathy, bilateral lung shadowing, and osteolytic changes in the 12th thoracic vertebra. Needle biopsy showed poorly differentiated carcinoma, positive human epidermal growth factor receptor 2, and positive androgen receptor, which suggested salivary duct carcinoma. These findings indicated a diagnosis of submandibular carcinoma T4aN2bM1 stage IVC. Pembrolizumab monotherapy was started, and tumor shrinkage was observed after three courses of treatment. At 1 year, complete response was achieved without adverse events, and treatment is ongoing. Despite a lack of evidence for the efficacy of immune checkpoint inhibitors in salivary gland carcinoma, the present case suggests that some patients might respond to this treatment. Hence, clinical trials are warranted.

Clinical Utility of Fine-Needle Aspiration Cytology for Adenoid Cystic Carcinoma of the Trachea with Thyroid Invasion: A Case Report.

BACKGROUND: Adenoid cystic carcinoma of the trachea (ACCT) is a rare cancer; ACCT with thyroid invasion is particularly rare. We first suspected anaplastic thyroid carcinoma (ATC) but diagnosed ACC after performing fine-needle aspiration cytology (FNAC). Tracheal origin was confirmed postoperatively. CASE DESCRIPTION: A 77-year-old woman presented to our hospital with acute inspiratory dyspnea requiring emergency tracheotomy. Physical examination revealed swelling of the right anterior neck and a hard, immobile mass. Computed tomography (CT) and ultrasonography (US) showed tumor extension to the right thyroid lobe and between the first and third tracheal rings, which caused severe stenosis of the lumen. We performed FNAC. Clinical findings were highly suggestive of ACCT with thyroid invasion. She underwent total laryngectomy, cervical esophagectomy, and thyroidectomy with bilateral selective neck dissection at another hospital. The tumor was located in the right posterior wall of the trachea and extended into the right thyroid gland. Pathological examination showed infiltrative carcinomatous proliferation with tubular and cribriform patterns. The tumor was classified as pT4N1. A definite diagnosis was made after histopathological analysis of the surgical specimen confirmed ACCT. The tumor was positive for FABP7, a putative prognostic marker of ACC, and metastasized to the lungs 3 years after surgery. CONCLUSIONS: ACCT with thyroid invasion is an extremely rare malignant neoplasm. FNAC was useful for differentiating ACCT from other diagnoses and enabled appropriate surgical treatment.

Trapezius muscle branch of the spinal accessory nerve without penetrating the sternocleidomastoid muscle as a pitfall in neck dissection: prevalence in a Japanese institution and a protocol for the prevention of iatrogenic injury.

BACKGROUND: The spinal accessory nerve (SAN) has several anatomical variations, which may be a pitfall in neck dissection (ND). These include the trapezius muscle branch (TB), which stems from the common trunk before entering the sternocleidomastoid muscle (SCM). AIMS/OBJECTIVES: To investigate the prevalence of this variation and suggest a protocol for preventing unexpected injury of the TB in ND. MATERIALS AND METHODS: We conducted a retrospective cohort study for 93 patients who had undergone neck dissection (117 sides) without resection of the SCM nor SAN. We recorded the division of the TB after and before penetration of the SCM by the common trunk (penetrating type TB [PTB]) and non-penetrating type TB [NPTB], respectively). RESULTS: Among NDs, PTB and NPTB were observed in 61 (52%) and 56 (48%) sides, respectively. In the subgroup of 24 cases with bilateral ND, PTB/PTB, NPTB/NPTB, and NPTB/PTB were observed in eight (33%), nine (38%), and seven (29%) cases, respectively. The prevalence of PTB/NPTB did not differ according to age, sex, or laterality. CONCLUSIONS AND SIGNIFICANCE: NPTB is a common anatomical variation. The presence or absence of a branch from the common trunk must be initially checked to avoid unexpected damage to the TB.

A mucin-rich variant of salivary duct carcinoma with a prominent mucinous component, a tumor that mimics mucinous adenocarcinoma.

The mucin-rich variant of salivary duct carcinoma (mSDC) is a rare type of salivary duct carcinoma. mSDC usually has both conventional SDC and mucinous adenocarcinoma-like areas. This article describes a first case of mSDC in which 95% of the tumor consisted of a mucinous area without no solid conventional SDC, so that the tumor mimicked mucinous adenocarcinoma. A 55-year-old man was evaluated for a 14 mm mass in the left submandibular gland. The tumor showed that floating tumor nests in a prominent mucinous lake. Some floating tumor nests had focal cribriform pattern with comedo necrosis, and all tumor cells had immunoreactivity for androgen receptor, gross cystic disease fluid protein 15, and Her-2/neu. A diagnosis of mSDC was rendered. mSDC with prominent mucinous component sometimes resembles mucinous adenocarcinoma. Identifying specific histological and immunohistochemical features of floating tumor nests in the mucinous area are important for the diagnosis.

Surgical management of tongue cancer during pregnancy.

There are ethical dilemmas in managing head and neck cancers during pregnancy. Diagnostic and treatment modalities need to be carefully determined. We herein describe 3 cases of tongue cancer during pregnancy. The details of the management would contribute to the daily practices for head and neck cancers. All three patients were Japanese female patients, two of them were 29 years old and one was 26 years old. All patients were admitted to the Nippon Medical School Hospital during pregnancy, complaining of oral pain and/or discomfort. Case 1 was diagnosed as tongue cancer stage T3N0M0, however, the tumor was superficial and controllable by partial glossectomy. Case 2 was stage T2N0M0 with deep invasion with ulcer, and the hemi-glossectomy with neck dissection and the reconstruction was thought to be the standard modality. However, she underwent partial glossectomy in order to reduce the stress of the fetus. Case 3 could not be diagnosed on admission by biopsy and she underwent partial glossectomy after delivery. In case 3, the pathological diagnosis was pT1 tongue cancer. In case 1 and case 3, the patient and baby were healthy. In case 2, however, the patient died of recurrence at the primary site. In decision making of the strategy, the most important factors are not only oncological evaluation but also ethical and emotional factors.

Three cases of carcinoma of the hypopharynx developing as metachronous second primary cancers after total laryngectomy with radiotherapy for carcinoma of the larynx.

We describe 3 cases of metachronous hypopharyngeal cancer developing after laryngeal cancer had been treated with both radiotherapy and total laryngectomy. All 3 patients were men, 2 were 89 years old, and 1 was 65 years old. All patients had undergone total laryngectomy and radiotherapy for cancer for the glottis more than 20 years earlier. All patients underwent total hypopharyngectomy with jejunal free flap reconstruction. Surgery was complicated by scars from previous cancer treatment, and highly sophisticated surgical skills are needed, especially for preparing the recipient vessels. The postoperative period was largely uneventful and without fatal complications, however, 2 of the 3 patients died of distant metastasis 22 months and 31 months after surgery.

Nasal polyp fibroblasts produce MIP-3alpha in response to toll-like receptor ligands and cytokine stimulation.

OBJECTIVE: Dendritic cells (DCs) play important roles in the development and perpetuation of immune responses. DCs are present in upper airway diseases such as chronic rhinosinusitis with nasal polyps. However, the mechanisms of how DCs migrate into the upper airway mucosa during upper airway inflammatory diseases remains unclear. Macrophage inflammatory protein-3alpha (MIP-3alpha) is known to be a migratory factor for immature DCs. There have been very few reports regarding cells producing this chemokine in the airways. To investigate this, we stimulated fibroblasts cultured from the nasal polyps with various toll-like receptor (TLR) ligands, which are derived from microorganisms, and IL-beta1 and TNF-alpha, which are proinflammatory cytokines, and analyzed their ability to produce MIP-3alpha. METHODS: Fibroblast lines were established from nasal polyps and stimulated with TLR2, 3, 4, 5, 7/8 and 9 ligands, IL-beta1 and TNF-alpha. MIP-3alpha mRNA expression in nasal polyp fibroblasts (NPF) was evaluated by real-time RT-PCR and the protein levels of MIP-3alpha in the supernatants of stimulated NPF was measured by ELISA. RESULTS: Stimulation with TLR2, 3, 4 and 5 ligands, IL-beta1 and TNF-alpha, induced MIP-3alpha gene expression and protein production in the cultured NPF This response was dose- and time-dependent. CONCLUSION: NPF possibly play an important role in the recruitment of DCs in upper airway diseases such as chronic rhinosinusitis with nasal polyps through the production of MIP-3alpha.

Combined stimulation with Poly(I:C), TNF-alpha and Th2 cytokines induces TARC production by human fibroblasts from the nose, bronchioles and lungs.

BACKGROUND: Th2 cells trigger allergic diseases in the respiratory tract. However, the mechanisms that cause Th2 cell infiltration remain unclear. Viral infections exacerbate allergic diseases in the respiratory tract. Thymus- and activation-regulated chemokine (TARC) recruits Th2 cells to sites of inflammation. Resident fibroblasts are thought to contribute to inflammatory cell infiltration through chemokine production. We compared the abilities of nasal, bronchiolar and lung fibroblasts to produce TARC. METHODS: Expression of TARC mRNA was evaluated by real-time RT-PCR, while the amount of TARC in supernatants was measured by ELISA. RESULTS: Costimulation with TNF-alpha and Th2 cytokines (IL-4, IL-13) or with poly(I:C) and Th2 cytokines (IL-4, IL-13) induced TARC production by nasal (polyp and normal) fibroblasts. Costimulation with TNF-alpha and Th2 cytokines (IL-4, IL-13) also induced TARC production by both bronchiolar and lung fibroblasts, but costimulation with poly(I:C) and Th2 cytokines (IL-4, IL-13) caused no induction. Combined exposure of cells to poly(I:C), TNF-alpha and Th2 cytokines (IL-4, IL-13) resulted in substantial production of TARC by nasal and lung fibroblasts, but much less by bronchiolar fibroblasts. CONCLUSIONS: TARC is directly inducible in diverse fibroblast populations from the respiratory tract (nose, bronchioles and lungs), but the mechanisms and levels of TARC production differ. Fibroblasts in the respiratory tract may contribute to Th2 cell infiltration and viral-induced exacerbation of allergic diseases, such as allergic sinusitis, asthma and allergic lung inflammation.

One-year evaluation of combined treatment with an intranasal corticosteroid and montelukast for chronic rhinosinusitis associated with asthma.

OBJECTIVES: Chronic rhinosinusitis associated with asthma is often difficult to treat effectively with intranasal corticosteroids alone. Thus, the aim of this study was to evaluate the effectiveness of combination treatment with an intranasal corticosteroid and a leukotriene-receptor antagonist (montelukast) in reducing the size of nasal polyps. METHODS: The subjects of this study were 20 patients with chronic rhinosinusitis associated with adult-onset asthma, which was being treated with inhaled corticosteroids. All patients were treated with intranasal fluticasone propionate, 200 microg/day, and montelukast, 10 mg/day, for 1 year. The size of nasal polyps and the score of sinus shadows were assessed with nasal endoscopy and computed tomography (CT), respectively, before and after treatment. The peripheral blood eosinophil counts were also evaluated before and after treatment. RESULTS: Nasal polyps were significantly smaller after both 6 months (p<0.01) and 12 months of treatment (p<0.01) than before treatment. The decrease in the shadow score was statistically significant after both 6 months (p<0.01) and 12 months of treatment (p<0.01). Significant reductions in peripheral blood eosinophil counts were also seen after both 6 months (p<0.05) and 12 months of treatment (p<0.01). A significant correlation was found between the rate of change in the peripheral blood eosinophil count and that in the CT score after both 6 months (r=0.578, p=0.012) and 12 months (r=0.625, p=0.007). CONCLUSION: Combined treatment with intranasal fluticasone propionate and montelukast, for at least 1 year, is effective for chronic rhinosinusitis associated with adult-onset asthma.

Synergistic induction of thymic stromal lymphopoietin by tumor necrosis factor alpha and Th2 cytokine in nasal polyp fibroblasts.

BACKGROUND: Thymic stromal lymphopoietin (TSLP) is elevated in airway inflammatory diseases such as asthma and triggers dendritic cell-mediated activation of Th2 inflammatory responses. Although allergic chronic sinusitis is a Th2 inflammatory disease of the upper airway, the mechanism underlying the predominance of Th2 responses still has to be clarified. We investigated the expression of TSLP in cytokine-treated nasal polyp fibroblasts. METHODS: Fibroblast lines were established from nasal polyp tissues. Their expression of TSLP mRNA was evaluated by real-time reverse-transcription polymerase chain reaction. The amount of TSLP in the supernatants was measured by enzyme-linked immunosorbent assay. RESULTS: Nasal polyp fibroblasts have the capacity to produce TSLP in response to stimulation by tumor necrosis factor (TNF) alpha. Combined stimulation with TNF-alpha + a Th2 cytokine (IL-4 or IL-13) was synergistic for TSLP production by the nasal polyp fibroblasts. This response was time and dose dependent. The TNF-alpha + Th2 cytokine (IL-4 or IL-13)-induced TSLP production was strongly inhibited by interferon gamma but not by IL-10. CONCLUSION: These results suggest that nasal polyp fibroblasts play a role in the development and regulation of Th2-type inflammation in the upper airway by producing TSLP.

Poly(I:C) synergizes with Th2 cytokines to induce TARC/CCL17 in middle ear fibroblasts established from mucosa of otitis media with effusion.

CONCLUSION: These results suggest that middle ear fibroblasts contribute to the recruitment of Th2 cells into the middle ear by producing thymus and activation-regulated chemokine (TARC). OBJECTIVES: Intractable otitis media is more common in atopic subjects and asthmatics than in the otherwise normal population. Although type 2 T helper (Th2) cytokines play crucial roles in the middle ear of these populations, the mechanism underlying the predominance of Th2 cytokines has yet to be clarified. TARC has been known to facilitate recruitment of Th2 polarized cells, resulting in high levels of Th2 cytokines in the middle ear. We investigated whether middle ear-derived fibroblasts produce TARC when stimulated with poly(I:C) and Th2 cytokines (IL-4, IL-13). MATERIALS AND METHODS: Fibroblast lines were established from middle ear mucosa. TARC mRNA expression was evaluated by real-time RT-PCR. The amount of TARC in the culture supernatants was measured by ELISA. RESULTS: Poly(I:C) induced only TARC gene expression in middle ear-derived fibroblasts. Combined stimulation with poly(I:C) and Th2 cytokine (IL-4, IL-13) synergistically induced TARC production by the cultured middle ear-derived fibroblasts. This response was dose and time dependent.

Synergistic Induction of Macrophage Inflammatory Protein-3α;/CCL20 Production by Interleukin-17A and Tumor Necrosis Factor-α; in Nasal Polyp Fibroblasts.

BACKGROUND: : Accumulation of T cells and immature dendritic cells (DCs) is one of the characteristic features of nasal polyps. However, the question remains why these cells accumulate in nasal polyp tissue. Macrophage inflammatory protein-3α; (MIP-3α;/CCL20) is a chemokine involved in the migration of T cells and immature DCs into inflammatory tissue sites. Fibroblasts are a rich source of cytokines and chemokines. The objective of this study was to demonstrate the expression of MIP-3α;/CCL20 in nasal polyp fibroblasts after stimulation with proinflammatory cytokines such as interleukin-17 (IL-17) and tumor necrosis factor-α; (TNF-α;). METHODS: : Fibroblast lines were established from nasal polyps. MIP-3α;/CCL20 mRNA expression was evaluated by real-time reverse transcription-polymerase chain reaction (real-time RT-PCR). The amount of MIP-3α;/CCL20 in the supernatants was measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: : IL-17A and TNF-α; synergistically induced MIP-3α;/CCL20 production by nasal polyp fibroblasts in a dose- and time-dependent manner. This synergy was observed by stimulation with TNF-α; plus IL-17A or IL-17F, but not IL-17E. CONCLUSIONS: : Nasal polyp fibroblasts, by producing MIP-3α;/CCL20, may play an important role in the recruitment of T cells and DCs in upper airway inflammatory lesions such as nasal polyps.

Combined stimulation of nasal polyp fibroblasts with poly IC, interleukin 4, and tumor necrosis factor alpha potently induces production of thymus- and activation-regulated chemokine.

OBJECTIVE: To examine the effects of cytokines and poly IC on the expression of thymus- and activation-regulated chemokine (TARC), a potent chemoattractant for helper T-cell type 2 (T(H)2) cells, in nasal polyp fibroblasts. DESIGN: Quantitative reverse transcription-polymerase chain reaction (RT-PCR) analysis. SETTING: Academic research. PARTICIPANTS: Primary fibroblast lines were established from human nasal polyp biopsy tissue specimens (n = 5) removed at polypectomy. MAIN OUTCOME MEASURES: The expression of TARC messenger RNA (mRNA) was evaluated by real-time RT-PCR. The amount of TARC in the supernatants was measured by enzyme-linked immunosorbent assay. RESULTS: Combined stimulation with interleukin 4 (IL-4) and tumor necrosis factor alpha (TNF-alpha) or with poly IC and IL-4 induced TARC production. Combined exposure of cells to poly IC, IL-4, and TNF-alpha resulted in substantial amounts of TARC release into the culture medium. Quantitative RT-PCR analysis revealed that simultaneous stimulation with those 3 compounds induced a tremendous increase in the amount of TARC mRNA in the nasal polyp fibroblasts. CONCLUSION: Nasal polyp fibroblasts contribute to T(H)2 cell infiltration and RNA virus-induced exacerbation of T(H)2-type airway inflammatory conditions such as allergic chronic sinusitis.

Toll-like receptor 2, 3, 4, 5 ligands and interleukin-4 synergistically induce TARC production in nasal polyp fibroblasts.

OBJECTIVE: Although type 2 T helper (Th2) cytokines such as IL-4 and IL-5 play a crucial role in the pathogenesis of chronic sinusitis with allergy, the mechanism underlying the predominance of Th2 cytokines has yet to be clarified. Thymus and activation-regulated chemokine (TARC) has been known to facilitate the recruitment of Th2 polarized cells, resulting in high levels of Th2 cytokines in the sinus mucosa as well as nasal polyps. The nasal and sinus cavities are ideal sites for studying the interplay between microbial Toll-like receptor (TLR) ligands and chemokines. We investigated whether nasal polyp fibroblasts produce TARC when stimulated with the breakdown products of microorganisms (TLR ligands) and a Th2 cytokine (IL-4). METHODS: Fibroblast lines were established from nasal polyp tissues. The expression of TARC mRNA was evaluated by real-time RT-PCR. The amount of TARC in the supernatants was measured by ELISA. RESULTS: Combined stimulation with TLR 2, 3, 4, 5 ligands and IL-4 induced TARC gene expression and protein production in the cultured nasal polyp fibroblasts. This response was time-dependent. CONCLUSIONS: These results suggest that nasal polyp fibroblasts contribute to innate immunity and may play an important role in the recruitment of Th2 cells into nasal polyps through the production of TARC.

Expression of MCP-4 by TLR ligand-stimulated nasal polyp fibroblasts.

CONCLUSION: These results indicate that nasal polyp fibroblasts contribute to innate immunity and eosinophilic inflammation such as nasal polyposis. OBJECTIVE: It is generally accepted that type 2 T helper (Th2) cytokines and some chemoattractants play an essential role in the pathogenesis of nasal polyposis. Nasal polyposis is characterized by chronic eosinophilic inflammation. The mechanisms that cause the predominance of eosinophilic infiltration in nasal polyposis have yet to be clarified. There is growing evidence that fibroblasts could be a major source of Th2 chemokines. Because the nasal and paranasal mucosae are the first respiratory tissues that environmental agents encounter, those tissues are exposed to injurious agents, including microorganisms and their breakdown products. We investigated whether nasal polyp fibroblasts produce a C-C chemokine, MCP-4, when stimulated with the breakdown products of microorganisms and a Th2 cytokine (interleukin (IL)-4). MATERIALS AND METHODS: Fibroblast lines were established from nasal polyp tissues. The expression of MCP-4 mRNA was evaluated by real-time RT-PCR. The amount of MCP-4 in the supernatants was measured by ELISA. RESULTS: TLR2, 3, 4 and 5 ligands, but not TLR7/8 or 9 ligands, induced small amounts of MCP-4. TLR2, 3, 4 and 5 ligands synergized with IL-4 to induce the production of MCP-4.

A case of meningeal carcinomatosis presenting with the primary symptoms of facial palsy and sensorineural deafness.

We report the case of a 59-year-old man with meningeal carcinomatosis (MC) who presented with peripheral facial palsy and progressive sensorineural deafness. The patient had been operated on for gastric cancer 1 year previously, and no metastases had been detected in the retroperitoneum or thorax at follow-up examination 1 year later. However, he developed headache, deafness, and peripheral facial palsy and was referred to us for further evaluation, as magnetic resonance of the head had shown no abnormalities. Ramsay Hunt syndrome was suspected, but no increase in the cerebrospinal fluid cell count was detected. On the other hand, the balance test suggested a central disorder. In addition, the plasma level of carcinoembryonic antigen suddenly increased, suggesting MC. The cerebrospinal fluid was examined several times; in the end malignant cells and an increase in the cell count were detected, and the diagnosis of MC was established.