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OBJECTIVES Vocal fold (VF) scarring and laryngeal stenosis are a significant clinical challenge. Excessive scar formation causes low voice quality or even life-threatening obstructions. Cytokines are thought to modulate multiple steps of the establishment of VF fibrosis, but there is no systematic report regarding their role in modulating VF fibrosis. This review aims to investigate the role of cytokines in modulating vocal fold fibrosis. STUDY DESIGN Literature review. METHODS This review searched for all relevant peer publications in English for the period 2009 to 2019 in the PubMed database using search terms: "laryngeal stenosis," "vocal fold scarring," and "cytokines." A thorough investigation of the methods and results of the reviewed studies was performed. RESULTS Comprehensive research in various studies, including analyses of prostaglandin E2 (PGE2), granulocyte-macrophage colony-stimulating factor (GM-CSF), hepatocyte growth factor (HGF), basic fibroblast growth factor (bFGF), transforming growth factor-β3 (TGF-β3), and interleukin-10 (IL-10), supports cytokine therapy for VF scarring and laryngeal stenosis to some extent. A few clinical studies on this topic support the conclusion that HGF and bFGF can be selected as effective drugs, and no serious side effects were found. CONCLUSIONS This review describes the potential of cytokines for modulating the process of VF fibrogenesis, although cytokines are still an unproven treatment method. As no ideal drugs exist, cytokines may be considered the candidate treatment for preventing VF fibrogenesis. Laryngoscope, 131:139-145, 2021.

Objective: Vocal fold scarring and laryngeal stenosis are major clinical challenges. Current drugs do not efficiently reduce scarring. We examined the antiproliferative and antifibrotic effects of cisplatin on primary human vocal fold fibroblasts (HVFFs). Methods: HVFFs were cultured in vitro and identified by immunocytochemistry. The relative viability of HVFFs was analyzed by Cell Counting Kit-8 assays (CCK-8). The fibrogenic phenotype was induced by transforming growth factor-β1 (TGF-β1) and reversed by cisplatin as shown by immunocytochemistry. Real-time PCR and Western blotting assessed collagen III and I. Western blotting for Smad2, p-Smad2, Smad-3, p-Smad3 and caspase-3 were performed. Results: CCK-8 results showed that cisplatin decreased the relative viability of HVFFs, and Western blots revealed elevation of the apoptosis-related protein caspase-3 in HVFFs. Cisplatin treatment reduced α-smooth muscle actin staining intensity in the presence of TGF-β1. Real-time PCR revealed the downregulation of collagen III and I in cisplatin-treated HVFFs. The TGF-β1-induced increased fibrogenic protein levels were decreased by cisplatin. Reduced levels were detected at late time points. Conclusions: Cisplatin induces antiproliferative and antifibrotic alterations in HVFFs. Cisplatin may prevent postoperative vocal fold scarring and laryngeal stenosis in patients treated with CO2 laser microsurgery and undergoing delayed wound healing.

Background and Objective Transoral laser surgery is useful for treating early glottic carcinoma. Wound areas after carbon dioxide (CO2) laser surgery are not covered by flaps, delaying healing. The healing process following laser cordectomy is not well understood. In this study, laryngoscopes were used to monitor the normal healing process after laser cordectomy and to determine if there was residual or recurrent disease. Materials and Methods This prospective case study included 36 patients who underwent CO2 laser surgery for early glottis carcinoma between January 2011 and June 2014 at a university tertiary referral center. Postoperative complications, oncologic results, and mucosal stabilization time were analyzed. Vocal fold stabilization was defined as an absence of gross changes during two consecutive follow-up examinations. Results The 3-year overall survival rate was 100% and the 3-year local control rate was 94%. Vocal cord stabilization was observed in 29 patients at a mean 88.1 days, with stabilization associated with the type of cordectomy (P

Transoral laser surgery is useful for treating early glottic carcinoma. Wound areas after carbon dioxide (CO2 ) laser surgery are not covered by flaps, delaying healing. The healing process following laser cordectomy is not well understood. In this study, laryngoscopes were used to monitor the normal healing process after laser cordectomy and to determine if there was residual or recurrent disease.This prospective case study included 36 patients who underwent CO2 laser surgery for early glottis carcinoma between January 2011 and June 2014 at a university tertiary referral center. Postoperative complications, oncologic results, and mucosal stabilization time were analyzed. Vocal fold stabilization was defined as an absence of gross changes during two consecutive follow-up examinations.The 3-year overall survival rate was 100% and the 3-year local control rate was 94%. Vocal cord stabilization was observed in 29 patients at a mean 88.1 days, with stabilization associated with the type of cordectomy (P 0.05). During the wound-healing process, two patients experienced local recurrences. One had a persistent white patch for over 4 months and the other presented with a new mass in a non-operated area. Biopsies of both lesions showed recurrent disease. Postoperative complications included granulation in two patients and anterior commissure adhesion in one.CO2 laser microsurgery is an effective treatment for early glottis carcinoma. Close attention should be paid to delays in healing process after laser surgery. Interventions should be considered for patients with abnormal laryngoscopic appearance or overly prolonged healing. Lasers Surg. Med. 48:483-489, 2016. © 2016 Wiley Periodicals, Inc.

Reconstruction of hypopharynx after tumor resection remains a challenging problem for the head and neck surgeons. A new surgical technique was introduced to reconstruct the hypopharynx after tumor resection using the superficial temporal artery flap. Three patients with T3 carcinoma of the posterior hypopharyngeal wall who underwent surgical resection of the tumor with laryngeal preservation were reported using this method. The larynx functions were preserved successfully in all the patients. In all patients, the nasogastric tubes were removed within 20-50 days (mean 33 days). The tracheal tubes were plugged on days between 14 and 44 (mean 26th day) postoperatively. Then all patients received the postoperative radiotherapy. The tracheal tubes were removed successfully 5-7 months after surgery (mean 6 months) without the evidence of apnea. The speech function was excellent in all patients, which was evaluated according to the voice-related quality of life questionnaire. Although lymph node metastasis was detected in one patient 6 months after surgery, there were no evidences of flap complications in all the three patients. The superficial temporal artery flap is a new option for the posterior pharyngeal wall reconstruction in selected cases with the hypopharynx carcinoma. The larynx functions were preserved successfully.

We report a 16-year-old female with Melnick-Needles syndrome complicated with severe obstructive sleep apnea-hypoxia syndrome.An overnight sleep study demonstrated that the patient had severe obstructive sleep apnea with an apnea-hypopnea index of 95/h. The lowest oxygen saturation was only 34%. The distraction osteogenesis technique was used to lengthen her mandible for the reconstruction of her upper airway.Postoperative panorex showed that the bilateral body of her mandible had been distracted about 16 mm singulorumly in the end of our distraction. Lateral radiograph revealed that the diameter of oral pharynx widen nearly 5 mm. The patient recovered after the upper airway reconstruction.

Melilotus extract has been used as a folk medicine in inflammation-related therapy. This study was undertaken to determine the potential benefits of this herbal extract in treating postoperative ecchymosis and edema after simultaneous rhinoplasty and blepharoplasty.Augmentation rhinoplasty and double-eyelid blepharoplasty were performed in one procedure by the same surgeon on 46 patients.Postoperative edema and ecchymosis were evaluated independently by two investigators checking the upper eyelid, lower eyelid, and paranasal area at postoperative days 1, 4, and 7. Our data showed that the patients receiving melilotus extract (n = 16) had lower scores not only in upper-eyelid and lower-eyelid ecchymosis, but also in paranasal ecchymosis at postoperative day 7 when compared with those in the control group. No significant difference in postoperative ecchymosis was detected in the group receiving dexamethasone treatment (n = 16) when compared with the control group (n = 14) at postoperative days 1, 4, and 7. The mean scores of upper-eyelid, lower-eyelid, and paranasal edema at postoperative days 1 and 4 were significantly lower in the group receiving dexamethasone treatment (n = 16) than that in the control group. Although the scores of eyelid edema reduction in the patients receiving melilotus extract showed no difference when compared with the control group, paranasal edema was reduced much more at postoperative days 4 and 7 when compared with the control group.We suggest the appropriate use of melilotus extract based on its beneficial effects on the postoperative results after simultaneous rhinoplasty and blepharoplasty.

Conclusions. Infiltration and activation of eosinophils is a characteristic of nasal polyposis. Allergic reaction is a risk factor for the accumulation of eosinophils in this disease. T-cell-derived interleukin 5 (IL-5) and autosecretion of IL-5 from activated eosinophils may be causative reasons for the extension and persistence of eosinophil inflammation. Objectives. To investigate whether eosinophils were accumulated and activated in nasal polyposis, and the roles of IL-5, eotaxin, and T cells in this process. Materials and methods. A retrospective study was conducted on 17 tissue samples from patients with nasal polyposis with allergy and 26 cases of non-allergic polyposis. Immunohistochemical staining by specific antibodies was carried out using the alkaline phosphatase anti-alkaline phosphatase method and the avidin-biotin complex technique.Results. The number of EG1-positive cells (pan eosinophil marker) was similar to the number of EG2-positive cells (activated eosinophil marker) in all tissue samples, although EG1- and EG2-positive cells were richer in allergic patients than those in non-allergic patients. Both EG1- and EG2-positive cells were correlated with CD3-positive cells (pan T cell marker) and IL-5-producing cells in allergic or non-allergic polyposis. A large proportion of IL-5 producing cells were eosinophils. Eotaxin protein was detected in all tissue samples and dominantly located in epithelial cells. Eotaxin expression between allergic and non-allergic subjects was not significantly different.

BackgroundIn nasal inverted papilloma (IP) and its malignant transformation process, abnormal cell growth has been regarded as an altered proliferation of the epithelial cells, while the role of programmed cell death in this process remains to be determined.MethodsAn apoptotic index was calculated, and the proliferation ability by using Ki67 as a marker was evaluated in the study subjects, which consisted of 15 cases of nasal chronic sinusitis, 23 cases of nasal IP, 9 cases of nasal IP with dysplasia, 8 cases of nasal IP with squamous cell carcinoma (SCC), and 21 cases of primary SCC. In addition, expressions of apoptosis-related molecules p53, Bcl-2, Bax, and Fas were investigated also.ResultsThe result showed that the Ki67 index increased in IP and IP with dysplasia. The Ki67 value was further enhanced in SCC within IP and primary SCC. The apoptotic index was low in IP with dysplasia, IP with SCC, and primary SCC. Concerning the expression of apoptosis-related proteins, p53 protein accumulated in IP with dysplasia, IP with SCC, and primary SCC. The p53 overexpression was directly correlated with the Ki67 index in IP and primary SCC diseases. No remarkable differences were found regarding expression of Bcl-2 and Fas productions among these diseases, and Bax protein was decreased only in primary SCC.ConclusionWe concluded that inhibition of apoptosis could be an early sign of IP undergoing malignant transformation. A high proliferative rate was a characteristic of IP-associated malignant diseases.

Most primarily cultured laryngeal squamous cell carcinoma cells are difficult to propagate in vitro and have a low survival rate. However, in our previous work to establish a laryngeal squamous cell carcinoma cell line, we found that laryngeal cancer-associated fibroblasts appeared to strongly inhibit the apoptosis of primarily cultured laryngeal squamous cell carcinoma cells in vitro. In this study, we investigated whether paired laryngeal cancer-associated fibroblasts alone can effectively support the growth of primarily cultured laryngeal squamous cell carcinoma cells in vitro. In all, 29 laryngeal squamous cell carcinoma specimens were collected and primarily cultured. The laryngeal squamous cell carcinoma cells were separated from cancer-associated fibroblasts by differential trypsinization and continuously subcultured. Morphological changes of the cultured laryngeal squamous cell carcinoma cells were observed. Immunocytofluorescence was used to authenticate the identity of the cancer-associated fibroblasts and laryngeal squamous cell carcinoma cells. Flow cytometry was used to quantify the proportion of apoptotic cells. Western blot was used to detect the protein levels of caspase-3. Enzyme-linked immunosorbent assay was used to detect the levels of chemokine (C-X-C motif) ligand 12, chemokine (C-X-C motif) ligand 7, hepatocyte growth factor, and fibroblast growth factor 1 in the supernatants of the laryngeal squamous cell carcinoma and control cells. AMD3100 (a chemokine (C-X-C motif) receptor 4 antagonist) and an anti–chemokine (C-X-C motif) ligand 7 antibody were used to block the tumor-supporting capacity of cancer-associated fibroblasts. Significant apoptotic changes were detected in the morphology of laryngeal squamous cell carcinoma cells detached from cancer-associated fibroblasts. The percentage of apoptotic laryngeal squamous cell carcinoma cells and the protein levels of caspase-3 increased gradually in subsequent subcultures. In contrast, no significant differences in the proliferation capacity of laryngeal squamous cell carcinoma cells cocultured with cancer-associated fibroblasts were detected during subculturing. High level of chemokine (C-X-C motif) ligand 12 was detected in the culture supernatant of cancer-associated fibroblasts. The tumor-supporting effect of cancer-associated fibroblasts was significantly inhibited by AMD3100. Our findings demonstrate that the paired laryngeal cancer-associated fibroblasts alone are sufficient to support the primary growth of laryngeal squamous cell carcinoma cells in vitro and that the chemokine (C-X-C motif) ligand 12/chemokine (C-X-C motif) receptor 4 axis is one of the major contributors.

Introduction Oncologic resection of the head and neck malignant tumor often results in complex reconstructive problems that require a reliable flap to restore both the form and function in single-stage operation. The free flap transfer has revolutionized head and neck reconstruction. However, forehead flap pedicled with superficial temporal artery (STA) or supraorbital artery (SOA)/supratrochlear artery (STrA) is a new option for reconstruction of head and neck with its own specific advantages. Method The forehead flap was applied to reconstruct the defects of the posterior hypopharyngeal wall, external perioral skin and buccal mucosal, and nose and periorbital tissues after malignant tumor resection. Nine of the patients were reconstructed with forehead flap pedicled with STA, 7 of whom underwent postoperative radiation. Eight of the patients were pedicled with SOA (and/or STrA), 1 of whom underwent postoperative radiation. Results We applied this method in a total of 17 male patients. The mean age of patients was 61 years (range, 47-69 years) with a follow-up time of 12 to 180 months. The biggest defect covered by forehead flap pedicled with STA was measured 10.0 × 6.5 cm. The biggest defect covered by forehead flap pedicled with SOA and/or STrA was measured 9.0 × 7.0 cm. In all 17 patients, no vascular crisis happened and no partial or total flap necrosis was observed. All skin graft area and donor site healed well. No patient experienced flap strictures or fistulas after operation or after radiotherapy. No local recurrence developed during the follow-up time. Functions were assessed by specialist as optimal as no limitation of eyes or mouth opening, and no limitation of food swallowing. Conclusions The forehead flap provides thin pliable tissue with reliable blood supply and high tolerance to radiotherapy. These advantages make it a valuable option to simultaneously reconstruct the defects after head and neck malignant tumor resection in certain selected patients.

Background: Apoptosis, which is regulated by both cell survival and death signals, is important for the swift clearance of unwanted cells. Objective: We sought to elucidate whether eosinophilic apoptosis is associated with tissue eosinophilia and to determine its resolution in allergic sinusitis (AS). Methods: Numbers of eosinophils, numbers of IL-5 + cells, and the apoptosis index of eosinophils were calculated in the submucosa (both superficial and deep layers) of patients with AS by using histochemical methods before and after prednisolone treatment. Patients without AS were used for control groups. Anti-EG2 antibody was used to identify eosinophils. IL-5, Fas, or Bax expression of eosinophils was evaluated to elucidate the role of the factors affecting eosinophilic apoptosis. Results: EG2 and IL-5 + cells were abundant in the submucosa of patients with AS, especially in the superficial layer. About 50% to 60% of the IL-5–producing cells were eosinophils. Apoptotic eosinophils were less numerous in the superficial layer than the deep layer in these diseases. After prednisolone treatment, an induction of eosinophilic apoptosis was accompanied by a significant decrease in the number of EG2 + and IL-5 + cells. No remarkable difference was observed in the Fas or Bax expression of eosinophils after prednisolone treatment. Conclusion: Autocrine secretion of IL-5 from eosinophils may be one reason why eosinophilic disease is difficult to manage. Induction of eosinophilic apoptosis is critical for reversing tissue eosinophilia in patients with AS. (J Allergy Clin Immunol 2000;106:551-8.)

Modulation of apoptosis may potentiate the sensitivity of tumor cells to chemotherapeutic agents, thus improving the clinical outcome of cancer treatment. Bax, an apoptosis-promoting member of the bcl-2 family, may be a key factor influencing the chemosensitivity of tumor cells, however, its involvement in cellular sensitivity to anti-cancer drugs remains uncertain in squamous cell carcinoma (SCC). To investigate the role of bax gene expression in modulating cisplatin (CDDP)-induced apoptosis in vitro, an established CDDP-resistant human head and neck SCC (IMC-3 cell line) was transfected with bax gene-bearing mammalian expression vector. Overexpression of the bax gene in CDDP-resistant IMC-3 cells elevated the CDDP susceptibility of tumor cells to a level similar to that of the parental IMC-3 cells. In an in vivo study, percutaneous transfer of apoptosis-promoting bax gene by particle-mediated (gene gun) delivery caused overexpression of Bax in SCC, which was confirmed by immunohistochemical staining, and inhibited the growth of mouse CDDP-resistant SCC. Furthermore, combination therapy with bax gene transfer and subcutaneous administration of CDDP at 3-day intervals markedly inhibited the growth of mouse SCC. Thus, overexpression of bax in SCC by a gene gun system appears to be a rational approach to improving the efficacy of chemotherapy and treatment outcome. We suggest that exogenous bax expression may have therapeutic applications for enhancing chemotherapy in SCC.

p27Kip1, a cyclin-dependent kinase inhibitor, is a negative regulator of the cell cycle, and apoptosis is a genetically encoded program of cell death. To clarify the relationship between the cell cycle and apoptosis, we investigated expression of p27, cyclin D1 and apoptosis-related proteins (p53, Bax, Bcl-2 and c-Myc) in 60 cases of oral and oropharyngeal squamous-cell carcinoma (SCC) using an immuno-histochemical approach, and evaluated spontaneous apoptosis in vivo. Our most notable finding was that spontaneous apoptosis in the p27-positive group was significantly higher than that in the p27-negative group (p = 0.028). In addition, the percentage of p27-positive cells was clearly correlated with that of Bax-positive cells (gamma = 0.288, p = 0.028) and with that of cyclin D1-positive cells (gamma = 0.416, p = 0.002). Expression of p27 was inversely associated with the clinical stage of total tumor progression (p = 0.027). However, no correlation was found between p27 expression and the following parameters: gender, tumor size, lymph node metastasis, overall survival and disease-free survival. Our results give evidence that the action of the cell-cycle regulator p27 is closely linked with apoptosis in clinical samples from patients and indicate that over-expression of p27 might induce apoptosis in cancer cells through elevation of Bax expression, thereby acting on tumor progression.

We investigated the expression of apoptosis-related factors, p53, Bax, Bcl-2, and spontaneous apoptosis in 57 cases of oral and oropharyngeal squamous cell carcinoma (SCC) by immunochemical staining and ApopTag kit. Positive expression of Bax was inversely associated with advanced tumor stage (P = 0.0225), lymph node metastasis (P = 0.0225), clinical stage (P = 0.0083) and poor prognosis (P = 0.0478). Positive expression of p53 was related to poor prognosis (P = 0.0445) and was associated with negative expression of Bax (P = 0.0439). The apoptosis index did not correlate with clinical outcome. These results suggest that abnormality of Bax expression plays an important role in tumor progression in oral and oropharyngeal SCC.

Objective: A cyclin-dependent kinase inhibitor, p27 kip1 , is recognized as a negative regulator of the cell cycle. To clarify whether immunohistochemical detection of p27 might provide prognostic information, we investigated the expression of p27 in laryngeal squamous cell carcinoma (SCC). Study Design: A retrospective study of patients was performed in 109 cases of laryngeal SCC. In addition, we investigated the expression of p53 and granulocyte colony-stimulating factor receptor (GCSF-R) to examine the prognostic significance of them in the same samples. Methods: Immunohistochemical staining by specific monoclonal antibodies was performed using the avidin-biotin-peroxidase complex technique. Results: Advanced tumor size and clinical stage and the occurrence of lymph node metastasis were associated with the absence ofp27 expression, but not correlated with p53 expression and GCSF-R expression. The overall 5-year survival rate in the p27-positive group was significantly higher than that in the p27-negative group. In the Cox proportional hazard model, p27 was demonstrated to be the most powerful prognostic factor among gender, tumor size, lymph node metastasis, stage of disease, and p53 and GCSF-R expression. Conclusions: We concluded that assessment of p27 expression is useful as a prognostic factor for laryngeal SCC and of value in selecting patients with laryngeal SCC for aggressive therapy.

BACKGROUND Interleukin-10 (IL-10) has been implicated as an important modulator of lymphoid cells, and its sequence is homologous to an open reading frame in the Epstein–Barr virus (EBV) genome. Nasopharyngeal carcinoma (NPC) is a representative tumor related to EBV infection. METHODS The authors investigated the expression of IL-10 in 21 primary NPCs by using an immunohistochemical approach to examine its prognostic significance. RESULTS IL-10 staining was positive in 12 of 21 primary NPCs (57%). There was no association between IL-10 expression and gender, tumor size, the occurrence of lymph node metastases, clinical stage, or recurrence. However, there was a significant difference in overall survival between the negative expression and positive expression of IL-10 (P = 0.0348). Although 87.5% of the IL-10 negative group survived for 5 years, only 15.6% of IL-10 positive patients survived for that length of time by the Kaplan–Meier method. IL-10 expression was significant as an independent prognostic indicator of overall survival by multivariate analysis using the Cox proportional hazards model (odds ratio, 26.64; P = 0.0019). CONCLUSIONS The results imply that expression of IL-10 is a prognostic factor in patients with NPC and may prove valuable in selecting patients with NPC who are candidates for aggressive therapy. Cancer 1999;85:1439–45. © 1999 American Cancer Society.

We investigated the expression of IL-10 in oral and oropharyngeal squamous cell carcinoma (SCC) specimens by an immunohistochemical technique. Of 58 SCC, 13 (22%) and 35 (60%) cases showed intense and moderate positive staining of IL-10, respectively. There was no association between the staining of IL-10 and clinicopathological features. However, the patients with intense staining of IL-10 had a significantly lower overall survival rate than those with moderate or negative staining of IL-10 (P = 0.019). In addition, the patients with intense staining of IL-10 had the highest score of platelet-derived endothelial cell growth factor (PD-ECGF), which is established as a poor prognostic indicator (P = 0.0105). These results suggested that IL-10 contributes to the clinical outcome of oral and oropharyngeal SCC.

Tunicamycin (TM), a naturally occurring antibiotic, blocks the first step in the biosynthesis of N-linked oligosaccharides in cells. In this study, we investigated whether changes in N-linked glycosylation affect the sensitivity of head-and-neck carcinoma cell lines to cis-diaminedichloroplatinum(II) (cisplatin) in vitro and in vivo. In vitro treatment of the IMC-3 and KB cell lines with TM significantly decreased the 50% inhibitory concentration (IC50) of cisplatin, as determined by the MTT assay (24.15 to 10.97 microg/ml, p 100 to 14.4 microg/ml, p < 0.05) to levels similar to those against parental IMC-3 cells. TM treatment decreased the number of Con A- and L-PHA-binding sites on the surface of tumor cells but had no effect on the intracellular platinum concentration. Induction of apoptosis in vitro by TM plus cisplatin in combination was increased compared with that by cisplatin alone. Furthermore, in vivo administration of TM plus cisplatin in combination significantly inhibited local tumor growth in the cisplatin-resistant in vivo C3H/He mouse model as compared with the control group (p < 0.05) and increased in vivo apoptosis of tumor cells. Our results suggest that the manipulation of glycosylation by TM in tumor cells might be a useful therapeutic strategy for successful chemotherapy using cisplatin against head-and-neck cancer.

To review the diagnosis, treatment and prognosis of olfactory neuroblastoma.Clinical data were retrospectively reviewed in 10 cases of olfactory neuroblastoma admitted from 1998 to 2002, including data of transmission electron microscopic (TEM) observation in 4 cases. According to Kadish's classification, 2 cases were in stage A, 4 in stage B and 4 in stage C. Three patients were treated with surgery alone, 7 with combined surgery and radiation.Among 10 cases, the overall 5-year survival rate was 60 %(6/10); 3 patients died from local recurrence, 1 lost follow-up. TEM demonstrated granules in the cytoplasm of 3 patients.The combined surgery and radiation can achieve excellent local control. Transmission electron microscope is important for its diagnosis.

To compare endoscopic approach with lateral rhinotomy for treatment of the sinonasal inverted papilloma in terms of advantage, indications and limitations of the procedures.Eighty-six cases with inverted papilloma were reviewed retrospectively, among which 23 cases underwent transnasal endoscopic procedures including 10 combined with Caldwell-Luc intervention, and 63 cases underwent lateral rhinotomy. The follow-up period ranged from 11 - 36 m (mean 23 m). The data were processed statistically by SPSS 10.0 software.Both procedures permitted removal of most sinonasal inverted papilloma. The endoscopic surgery provided an excellent visualization, and preserved a vital anatomic structure and left no facial scar. Lateral rhinotomy was associated with postoperative facial scar or deformity. The recurrence rate in lateral rhinotomy group was 9.5% and in endoscopic approach was 13% (P0.05).Endoscopic approach is favored for the treatment of non-massively extending sinonasal inverted papilloma because of an acceptable recurrence and a better cosmetic results.

Cancer-associated fibroblasts (CAFs) play a crucial role in cancer progression and even initiation. However, the origins of CAFs in various cancer types remain controversial, and one of the important hypothesized origins is through epithelial-mesenchymal transition (EMT) from cancer cells. In this study, we investigated whether the HEp-2 laryngeal cancer cells are able to generate CAFs via EMT during tumor formation, which is now still unknown. The laryngeal xenografted tumor model was established by inoculating the HEp-2 laryngeal cancer cell line in nude mice. Primary cultured CAFs from the tumor nodules and matched normal fibroblasts (NFs) from the adjacent connective tissues were subcultured, purified, and verified by immunofluorescence. Migration, invasion, and proliferation potentials were compared between the CAFs and NFs. A co-culture of CAFs with HEp-2 cells and a co-injection of CAFs with HEp-2 cells in nude mice were performed to examine the cancer-promoting potential of CAFs to further verify their identity. Karyotypic analyses of the CAFs, NFs, and HEp-2 cells were conducted. A co-culture of NFs with HEp-2 cells was also performed to examine the expression of activated markers of CAFs. A pathological examination confirmed that the laryngeal xenografted tumor model was successfully established, containing abundant CAFs. Immunocytochemical staining verified the purities and identities of the CAFs and NFs. Although the CAFs manifested higher migration, invasion, proliferation, and cancer-promoting capacities compared with the NFs, an analysis of chromosomes revealed that both the CAFs and NFs showed typical normal mouse karyotypes. In addition, the NFs co-cultured with HEp-2 cells did not show induced expressions of activated markers of CAFs. Our findings reveal that the CAFs in the HEp-2 established laryngeal xenografted tumor are not of laryngeal cancer origin but of mouse origin, indicating that the HEp-2 laryngeal cancer cells cannot generate their own CAFs via EMT in this model.

Reduction of p57(kip2) expression is related to carcinogenesis in laryngeal mucosa. Assessment of p57(kip2) expression may be a promising candidate as a progressive biomarker in laryngeal squamous cell carcinoma (SCC).To investigate the expression and significance of p57(kip2) in a dysplasia/carcinoma sequence of laryngeal mucosa.A retrospective study was performed involving 10 cases of normal mucosa, 31 of laryngeal leukoplakia and 109 of laryngeal SCC. p57(kip2) and p53 protein expression was detected in the tissue samples of these patients using immunohistochemistry.p57(kip2) expression was decreased in leukoplakia with moderate or severe dysplasia, and further decreased in SCC. No significant difference was found between normal mucosa and leukoplakia with no or mild dysplasia. In patients with laryngeal SCC, advanced tumor size and clinical stage and the recurrence of disease were associated with reduced p57(kip2) expression. The occurrence of lymph node metastasis was also related to negative expression of p57(kip2). The overall 5-year disease-free survival rate of patients with laryngeal SCC was significantly higher in the p57(kip2)-positive than in the p57(kip2)-negative group.

To investigate the expressions and significances of P57(kip2), p53 and hsp60 proteins in the dysplasia-carcinoma sequence of oral mucosa. A retrospective study was performed in 10 cases of normal oral mucosa, 79 cases of leukoplakia and 67 cases of squamous cell carcinoma (SCC). The expressions of P57(kip2), p53 and hsp60 proteins were detected in the tissue samples of these populations using immunohistochemical method. P57(kip2) expression was decreased in oral leukoplakia with moderate or severe dysplasia, and further decreased in oral SCC. Negative expression of P57(kip2) was significantly associated with advanced tumor size, the occurrence of lymph node metastasis and the advanced clinical stage in oral SCC. The overall 5-year survival rate in the P57(kip2) positive group was significantly higher than that in the P57(kip2) negative group. P57(kip2) expression was decreased in oral leukoplakia with moderate or severe dysplasia, and further decreased in oral SCC. It was a remarkable progressive and prognostic biomarker in oral SCC.