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With the growing acceptance of nonsurgical therapies for laryngeal squamous cell carcinomas (LSCCs), it has become important to delineate surgical salvage strategies for disease recurrences. Total laryngectomy is often recommended, but appropriately selected laryngeal recurrences may be treated successfully with partial laryngeal surgery: laryngeal function can be preserved with oncological efficacy. The main available studies dealing with partial laryngeal surgery in recurrent carcinoma were critically reviewed. The most appealing feature of salvage transoral laser surgery (TLS) is the opportunity to make tumor-tailored excisions without any reconstructive limitations and retaining the option to switch to open partial laryngectomy. A recent detailed review of 11 series found a pooled local control rate of 57% after a first TLS procedure. Supracricoid laryngectomy (SCL) seems to achieve good local control rates in selected cases of recurrent supraglottic-glottic carcinoma: one review considering seven series calculated that 85% of the patients treated with salvage SCL after radiotherapy experienced no local recurrence; and total laryngectomy after failure of salvage SCL afforded an overall local control rate of 65%. Neck dissection is mandatory in all cases of local LSCC recurrence with evidence of neck metastases, and routine elective neck dissection is recommended for recurrent supraglottic and transglottic cancers. [ABSTRACT FROM AUTHOR]

The article focuses on the use of orthotopic mouse model to analyze the laryngeal squamous cell carcinoma. It mentions that the animals were monitored through direct laryngoscopy and ultrasound for the survival and growth of tumor. It offers information on the phenotype and malignant behavior that creates its natural biologic behavior as of laryngeal cancer patients.

Background:A case of salvage supracricoid laryngectomy with cricohyoidoepiglottopexy after failed radiation therapy and vertical partial laryngectomy had successful oncological and functional outcomes. This is the first reported application of salvage supracricoid laryngectomy with cricohyoidoepiglottopexy after the failure of two major treatments.Case report:A 65-year-old man was referred for salvage supracricoid laryngectomy with cricohyoidoepiglottopexy. The right recurrent hemilarynx was successfully resected. After pexis, the right lobe of the thyroid gland was repositioned to overlap and reinforce the pexis gap and fill the devoid portion of the strap muscular closure. Multiple scattered foci (recurrent tumour–node–metastasis stage T2) were identified around the arytenoid cartilage and beneath the musculocutaneous flap. Four years after supracricoid laryngectomy with cricohyoidoepiglottopexy, the patient's recovery was following a favourable course and he had satisfactory laryngeal function.Conclusion:Appropriate case selection and proficient surgical skills were essential for a successful outcome. Head and neck surgeons should not be afraid to adopt functional preservation open surgical procedures in well-selected and well-motivated patients. A requirement for more challenging surgical procedures and meticulous rehabilitation processes should not exclude appropriate treatments from a surgeon's repertoire. [ABSTRACT FROM PUBLISHER]

Conclusions: Distant metastasis was a major pattern of recurrence after postoperative radiotherapy (PORT) for squamous cell carcinoma (SCC) of the oropharynx, hypopharynx, and larynx. PORT provided good loco-regional control, with tolerable toxicities. Advanced pT and pN were unfavorable prognostic factors. Objective: To determine the clinical outcomes, and the patterns and risk factors for recurrence of SCCs of the oropharynx, hypopharynx, and larynx treated with surgery and PORT. Methods: We retrospectively reviewed 84 patients who received PORT after definitive surgery for SCC of the oropharynx, hypopharynx, or larynx between 2000 and 2010. The primary sites were the oropharynx in 25 patients, hypopharynx in 47 patients, and larynx in 12 patients. Results: The 3-year overall survival (OS), progression-free survival (PFS), and loco-regional control (LRC) rates were 64.9%, 56.7%, and 92.1%, respectively. Recurrences were observed in 27 patients: 6 patients had loco-regional recurrence and 23 patients developed distant metastasis. On multivariate analysis, pT4 and pN2c-N3 displayed significantly worse effects on OS ( p = 0.02 and p < 0.01, respectively) and PFS ( p = 0.02 and p < 0.001, respectively). In the acute phase, 12 patients experienced grade 3 or 4 toxicities. There were no grade 5 toxicities. Late grade 3 toxicity developed in six patients and no grade 4 or 5 toxicities were observed. [ABSTRACT FROM AUTHOR]

Conclusion: Despite the low incidence of superior mediastinal metastasis (SMM) we recommend elective superior mediastinal dissection (ESMD) and close follow-up for all patients with laryngeal carcinoma involving the subglottis, because higher peristomal recurrence (PR) rates and lower survival rates were observed in the presence of SMM numerically even though statistical support was lacking. Background: This study was undertaken to identify the incidence of SMM and to evaluate the need for ESMD in laryngeal tumors involving the subglottis. Methods: Medical records of patients who had undergone total laryngectomy for laryngeal carcinoma were reviewed retrospectively and 68 patients (45 with ESMD and 23 without ESMD) who had pathologically proven subglottic involvement were included in the study. Results: SMM was found in 3 of 45 (6.6%) patients who underwent ESMD. The PR rate was higher in patients with SMM (66.7%) than in patients without SMM (9.5%) and the presence of SMM was significantly related to PR ( p = 0.043) in univariate analysis. However, this relationship was not preserved in multivariate analysis. The 3- and 5-year survival rates of patients with SMM were lower (both 66.7%) than patients without SMM (83.3% and 76.2%, respectively), but decreased survival rates did not differ statistically from the survival rates of 42 patients without SMM. [ABSTRACT FROM AUTHOR]

Summary Head and neck squamous cell carcinomas (HNSCC) are malignant tumors that arise from the surface epithelium of the oral cavity, oropharynx and larynx, primarily due to exposure to chemical carcinogens or the human papilloma virus. Due to their location, dental practitioners are well-positioned to detect the lesions. Deadlier than lymphoma or melanoma, HNSCC is incompletely understood. For these reasons, dental practitioners and researchers are focused on understanding HNSCC and the processes driving it. One of these critical processes is invasion, the degradation of the basement membrane by HNSCC cells with subsequent movement into the underlying connective tissue, blood vessels or nerves. Cancer cells metastasize to distant sites via the blood vessels, lymphatics and nerves. Metastasis is associated with poor survival. Since invasion is essential for development and metastasis of HNSCC, it is essential to understand the mechanism(s) driving this process. Elucidation of the mechanisms involved will facilitate the development of targeted treatment, thereby accelerating development of precision/personalized medicine to treat HNSCC. Robust in vitro and in vivo assays are required to investigate the mechanistic basis of invasion. This review will focus on in vitro and in vivo assays used to study invasion in HNSCC, with special emphasis on some of the latest assays to study HNSCC. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to investigate the expression of Notch1 in human laryngeal squamous cell carcinoma (LSCC) tissues and its relationship to clinicopathologic characteristics as well as their prognostic value in LSCC. Methods: Samples from 106 patients with LSCC were analyzed for Notch1 expression by immunohistochemical staining. The relationship between Notch1 expression and clinicopathologic parameters was subsequently analyzed. Univariate analysis and multivariate analysis of patient survival were examined using the Kaplan-Meier method and Cox proportional hazards model, respectively. Results: We found that Notch1 had positive expression in 71 of 106 cases of LSCC (66.98%), which was obviously higher than laryngeal normal tissues (P < .01) and significantly correlated with the clinical stage, lymph node metastasis, and histological grade (all Ps < .05). Univariate analysis revealed that Notch1 expression tended to show an unfavorable influence on overall survival (OS) and disease-free survival (DFS) (both Ps < .01). Multivariate analysis demonstrated that Notch1 was an independent prognostic factor for patients with LSCC (P < .05). Conclusion: These results reveal that Notch1 expression is a potential prognostic factor for malignant progression, metastasis, and survival of LSCC patients. Furthermore, it has been demonstrated that high expression of Notch1 was associated with unfavorable OS and DFS in LSCC patients. [ABSTRACT FROM AUTHOR]

Conclusions: Increased expression of Dicer may be a prognostic biomarker for patients with laryngeal squamous cell carcinoma (LSCC). Objectives: Recent studies have shown that many microRNAs (miRNAs) play an important role in the development and progression of human cancers. Dicer, one of the most important enzymes of the miRNA machinery, performs the final step of biogenesis of miRNAs. This study aimed to investigate the impact of Dicer expression on patient survival in human LSCC. Methods: We detected the expression of Dicer in larynx tissue specimens from 76 LSCC samples and 26 polyps by immunohistochemistry. The clinicopathological and prognostic significance of Dicer expression was investigated in LSCC. Results: Our data showed that the expression of Dicer was significantly higher in the LSCC than in the polyp tissue specimens. Moreover, the expression level of Dicer was significantly associated with the pTNM stage and tumor lymph node metastasis. Kaplan-Meier survival analyses revealed a strong association between tumor Dicer expression and the survival of the patients with LSCC. [ABSTRACT FROM AUTHOR]

Conclusion: Photodynamic therapy (PDT) is a viable and safe option for early laryngeal cancer that would be less suitably treated with radiation or trans-oral laser surgery (TLS). The cure rates with PDT appear to be comparable to those of conventional therapy, and the voice outcomes are also comparable. In the case of many sarcomas, PDT appears to be an organ- and function-sparing therapy, although it is more costly than other treatments. Objectives: The aim of this study was to show the results of PDT when it is used as a primary treatment of early laryngeal cancer. Methods: We studied the results of PDT when used as a primary treatment. We looked at survival, effect on tumor, side effects, voice, and costs. Results: The follow-up period was a median of 59 months. Nine of 10 patients were cured of their laryngeal cancer. PDT alone cured seven patients. All four of the sarcomas were cured using temoporfin. Two of three tumors that involved the anterior commissure were cured using only interstitial illumination with PDT. No serious side effects were noted. The patient's voices were improved after treatment in 5 of 10 cases, and none had a worsened voice. [ABSTRACT FROM AUTHOR]

Objectives. Metastasis of laryngeal squamous cell carcinoma (SCC) to the intra-abdominal gastrointestinal tract is exceedingly rare. The objectives of this case report are to describe a case involving a perforated metastasis of a laryngeal SCC to the ileum and to review the literature pertaining to other similar cases. Methods. A review of patient’s chart and a review of the English literature involving malignant SCC of the larynx with metastasis to the small bowel. Results. We describe the case of a 58-year-old man who had failed induction chemotherapy and underwent a laryngopharyngectomy with bilateral neck dissection and pectoralis major flap for a T4N2c laryngeal SCC. Subsequently, the patient was treated with postoperative radiation and cituximab. The patient went on to present with symptoms consistent with a ruptured appendix, supported by ultrasound imaging. The patient was taken to the operating room where a right hemicolectomy was performed. Pathological gross examination confirmed a 4 cm transmural perforation in the terminal ileum. Microscopy demonstrated deposits of metastatic squamous cell carcinoma in the surrounding smooth muscle. Metastatic carcinoma was also found in a separate nodule from the abdominal wall. The patient had an uncomplicated post-operative period, and survived several months thereafter. Conclusions. Metastasis of laryngeal SCC to the small bowel with perforation is exceedingly rare, but possible. These patients may be successfully managed with resection. [ABSTRACT FROM AUTHOR]

Conclusion: The epidermal growth factor receptor (EGFR) mutation is rare in patients with laryngeal squamous cell carcinoma (LSCC) in China. Objective: To determine the incidence of EGFR mutations in patients with LSCC who underwent surgical resection in mainland China. Methods: xTAG technology was used to detect the EGFR exon 19, exon 20, and exon 21 mutations in 132 patients with LSCC who underwent surgical treatment in our hospital from 2010 to 2013. Results: Of the 132 LSCC specimens examined, only 1 specimen was found to be positive for EGFR exon 20 mutation (0.76%). The mutation was p.T790M in exon 20. Two LSCC specimens were positive for EGFR exon 21 mutation (1.52%). The mutation was p.L858R in exon 21. None of the samples was found to be positive for EGFR exon 19 mutation. [ABSTRACT FROM AUTHOR]

Radiotherapy is one of the mainline treatments for cancer. One of the side effects associated with radiotherapy includes skin problems, which range from mild (dull erythema and tightening of the skin) to severe (moist desquamation resulting in open wounds that can be very painful associated with sloughy and, in some severe cases, necrosis). The increased use of advanced radical treatments, such as intensity-modulated radiotherapy treatment (IMRT), can also result in a higher number of patients experiencing skin reactions. It is estimated that approximately 87% of patients will experience a moderate-to-severe skin reaction (Harris et al, 2011) An evaluation was undertaken in 20 patients with head and neck cancer following a prescribed treatment of radiotherapy to compare a polymeric membrane dressing (PolyMem®) against the standard treatment. The standard treatment consisted of topical aqueous cream at the start of radiotherapy with the addition of paraffin gauze when moist desquamation occurred. A bespoke evaluation form was completed for a period of 4 weeks or until healed. Patients were asked to complete both qualitative descriptions and numerical scores of pain for symptoms and procedural pain. Analgesia and sleep patterns were logged and, in addition, free text diaries were provided for up to 4 weeks. Common themes were identified and qualitative data analysed. [ABSTRACT FROM AUTHOR]

Conclusion: Frontovertical partial laryngectomy is useful for treatment of T1 and T2 glottic squamous cell carcinoma with anterior commissure involvement. Objective: To evaluate the efficiency of frontovertical partial laryngectomy for T1 and T2 glottic carcinoma with anterior commissure involvement. Methods: This was a retrospective review of 58 cases of glottic squamous cell carcinoma with anterior commissure involvement (T1, n = 28; T2, n = 30) that were treated by frontovertical partial laryngectomy between August 2000 and August 2010. Results: Postoperative pathology reports confirmed negative tumor margins in every case. All patients were followed postoperatively, with a median follow-up interval of 55 months. Three patients had local recurrence; there were no patients who had cervical or distant metastases. The 3-year local control rate was 94% according to life tables curves. There were no reports of laryngostenosis or dysphagia in any patients, and mean Voice Handicap Index (VHI) questionnaire scores were 32.9. [ABSTRACT FROM AUTHOR]

Introduction:Complementary and alternative medicine usage, though rising, remains largely devoid of a sound scientific basis; however, there is increasing evidence to support its use in cancer therapy.Aim:To present the case of a patient with laryngeal carcinoma who made a full recovery following mistletoe therapy, despite failing to respond to chemoradiotherapy and salvage laryngectomy.Design:Case report with relevant literature review.Results:The patient developed extensive, unresectable stomal recurrence, and it was deemed appropriate to supply palliative care only. Following treatment with mistletoe extract injections after palliative radiotherapy, he recovered fully and was eventually discharged from care.Conclusion:The benefit of mistletoe in laryngeal cancer treatment requires further investigation, and might be considered in selected patients, as an adjunct or when other conventional therapies have failed. [ABSTRACT FROM PUBLISHER]

Background:The prevalence of occult neck metastasis in patients undergoing salvage total laryngectomy remains unclear, and there is controversy regarding whether elective neck dissection should routinely be performed.Method:A retrospective case note review of 32 consecutive patients undergoing salvage total laryngectomy in a tertiary centre was performed, in order to correlate pre-operative radiological staging with histopathological staging.Results:The median patient age was 61 years (range, 43–84 years). With regard to lymph node metastasis, 28 patients were pre-operatively clinically staged (following primary radiotherapy or chemoradiotherapy) as node-negative, 1 patient was staged as N1, two patients as N2c and one patient as N3. Fifty-two elective and seven therapeutic neck dissections were performed. Pathological analysis up-staged two patients from clinically node-negative (following primary radiotherapy or chemoradiotherapy) to pathologically node-positive (post-surgery). No clinically node-positive patients were down-staged. More than half of the patients suffered a post-operative fistula.Conclusion:Pre-operative neck staging had a negative predictive value of 96 per cent. Given the increased complications associated with neck dissection in the salvage setting, consideration should be given to conservative management of the neck in clinically node-negative patients (staged following primary radiotherapy or chemoradiotherapy). [ABSTRACT FROM PUBLISHER]

In this study, we report an extraordinary case in which a patient was diagnosed with laryngeal squamous cell carcinoma and simultaneous chronic lymphocytic leukemia. A 53-year-old male patient presented with hoarseness and a neck mass. Laryngeal examination revealed a lesion that had infiltrated the right band, cord, and ventricle, and the left cord and band. There were multiple bilateral lymphadenopathies in the supraclavicular, inguinal, and axillary regions, the largest of which was 4x4 cm. Following hematology consultation, a direct laryngoscopy and biopsy were performed. An excisional biopsy was taken from the neck mass. The postoperative histopathology reported an invasive squamous cell carcinoma in the larynx and a small B cell lymphoid leukemia in the neck. Following consultation with our oncology department, curative radiotherapy was applied to the neck region. Following this therapy, the mass was no longer detectable upon palpation, although no curative treatment was applied for leukemia. It is important to be aware that ymphadenopathy may be secondary to head or neck cancer or to a hematological malignancy. Thus, preoperative evaluation should be carefully performed, and hematological malignancy should be considered as a differential diagnosis when histopathologically evaluating neck dissection material. [ABSTRACT FROM AUTHOR]

Background Management of advanced laryngeal cancer is complex and ideal strategy is yet to be defined. This study evaluates the experience of a single head and neck oncologic centre in the management of T4 laryngeal cancer. Methods Retrospective assessment of cases primarily treated for T4a squamous cell carcinoma of the larynx, between 1980 and 2007, at a tertiary referral center. Results A total of 384 cases were studied. Five-year disease specific survival was 56.2% and local control 87.4%. Regional and distal control estimates were 90.3% and 88.3% respectively. Prognosis was significantly superior for cases treated with primary surgery compared to cases solely managed with non-surgical modalities. Positive surgical margins and regional disease worsened prognosis. Conclusion This study suggests that primary surgery remains a key element in the treatment of advanced laryngeal cancer. The need for well-designed, prospective, randomised studies in order to further evaluate the remaining role of primary surgery in the modern management of locally advanced laryngeal lesions is emphasized. [ABSTRACT FROM AUTHOR]

The aim of this study was an immunohistochemical assessment of the basement membrane antigen collagen IV (Col IV) in squamous cell carcinomas of the larynx and their respective nodal metastases. Forty radical laryngectomy specimens from 2009 to 2011 were randomly selected for this study. Tumor blocks were immunostained using the monoclonal antibody CIV 22 (Dako, Denmark). Col IV was evaluated using a semiquantitative morphometric method and graded according to its quantity and continuity. Col IV expression and epithelium-stroma interface (TESI) showed high significant differences between surface and deepness of larynx tumors. As for TESI, there was a strong relation between tumors with and without lymph node metastases. There was no correlation between desmoplasia and TESI disarrangement, but the latter had a high significant relation with histological grade. Col IV expression was independent of histological grading of the tumor. The results of the present study show an alterated distribution of collagen type IV with a significant loss in all cases of laryngeal cancer, reflecting tumor aggressiveness. [ABSTRACT FROM AUTHOR]

Objective:This study investigated the expression and functional effects, and related molecular mechanisms, of microRNA-519a in laryngeal squamous cell carcinoma.Methods:MicroRNA-519a and HuR messenger RNA in laryngeal squamous cell carcinoma were measured using reverse transcription polymerase chain reaction. MicroRNA-519a effects on the growth of human epithelial type 2 cells were tested using an MTT assay. The influence of microRNA-519a on the expression levels of HuR and other related genes in protein was tested by Western blotting. Cell cycle analyses were performed using flow cytometry. Associations between expression levels and patients' clinical parameters were analysed with Pearson correlation analysis.Results:Expression of microRNA-519a in laryngeal squamous cell carcinoma tissues was significantly lower than in adjacent non-cancerous tissues. The expression of microRNA-519a was negatively associated with histological differentiation, tumour–node–metastasis stage, lymphatic metastasis and disease-free survival time. After increasing the level of microRNA-519a in laryngeal squamous cell carcinoma human epithelial type 2 cells, cell growth was inhibited and cell cycle was arrested in the G2/M phase. MicroRNA-519a down-regulated HuR gene expression in protein levels without affecting messenger RNA levels.Conclusion:MicroRNA-519a may function as a tumour suppressor by inhibiting HuR expression, and may serve as a therapeutic target for laryngeal squamous cell carcinoma. [ABSTRACT FROM PUBLISHER]

Objective:To report and discuss the outcome of a treatment algorithm for patients with tumour stage 1 glottic squamous cell carcinoma.Method:A retrospective outcome analysis study was performed using data from a tertiary referral centre.Results:Sixty-nine patients were treated with radiotherapy and 26 with surgery, in accordance with the treatment algorithm. Five-year overall survival rates were the same for both treatment groups (92 per cent). Five-year disease-specific survival rates were 100 per cent for surgery, 98 per cent for radiotherapy and 99 per cent overall. The overall 5-year laryngeal preservation rate was 89.1 per cent, being 95.7 per cent for surgery patients and 86.7 per cent for radiotherapy patients (p = 0.502). There was no significant association between laryngeal preservation rates and age (p = 0.779), anterior commissure involvement (p = 0.081), tumour stage (1a or 1b) (p = 0.266) or treatment modality (surgery or radiotherapy; p = 0.220). There was no significant difference in local recurrence rates between the two treatment groups (19.3 per cent for radiotherapy vs 10.0 per cent for surgery; p = 0.220). The overall 5-year regional recurrence rate was 1.2 per cent.Conclusion:Tumour stage 1 glottic carcinoma can be managed with different treatment modalities, following an individualised treatment algorithm, with results comparable to published outcomes. [ABSTRACT FROM PUBLISHER]

Over 2,200 cases of carcinoma of the larynx are diagnosed in the UK annually, with an overall 5-year survival rate of 67%. Angiogenesis is vital for the growth and metastasis of solid tumours and the expression of key angiogenesis-related proteins has been shown to be of prognostic significance. In this study we reported the expression of key angiogenesis-related factors, selected from a pilot array study, in a cohort of laryngeal tumours and associated meta-static lymph nodes. Forty patients diagnosed with squamous cell carcinoma of the larynx were recruited. Tissue specimens were obtained intra-operatively, prior to chemo- and/or radiotherapy, from the tumours and secondary lymph nodes. The patient group comprised 32 men and 8 women with a mean age of 68 years (range, 51-89 years). The relative expression of the angiogenesis-related proteins angiogenin, interleukin (IL)-8, tissue inhibitor of metalloproteinases-1 (TIMP-1), vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF)-basic and insulin-like growth factor binding protein 3 (IGFBP3) was determined in the tissue lysates by ELISA. The expression of angiogenin was higher in early-stage compared with late-stage tumours (P=0.034) and the expression of IGFBP3 was higher in tumours compared with the metastatic lymph nodes (P=0.016). No statistically significant differences were recorded for VEGF, FGF, TIMP-1 or IL-8 between tumour stages or primary tumours and lymph nodes. To the best of our knowledge, this study was the first to investigate multiple angiogenic factors in the lysates of laryngeal carcinomas and metastatic nodes and identified angiogenin and IGFBP3 as factors possibly involved in tumour progression. A greater understanding of their function may offer novel prognostic and/or therapeutic options. [ABSTRACT FROM AUTHOR]

Conclusions: Immunoglobulin (Ig) M is overexpressed in laryngeal squamous cell carcinoma (LSCC), and its expression has an independent protective impact on disease-free survival in LSCC. Objective: A number of studies have reported on the ectopic expression of Ig in cancer cells, yet there has been a lack of understanding of its clinical and prognostic significance. This study aimed to investigate the expression of IgM in resected specimens of LSCC and to evaluate its clinical significance and prognostic value. Methods: Immunohistochemistry (IHC) and Western blotting were used to detect the expression of IgM in LSCC and normal laryngeal tissues. The serum level of IgM was also analyzed by immunoturbidimetric assay. Results: IHC and Western blot studies demonstrated that IgM was overexpressed in LSCC specimens ( p < 0.001), while the serum level of IgM in patients with LSCC was not different from healthy controls. Chi-squared analysis revealed that the expression level of IgM was negatively correlated with regional lymph node metastasis and tumor stage ( p = 0.011 and 0.025, respectively). Univariate analysis showed that IgM expression was significantly correlated with enhanced disease-free survival (DFS) ( p = 0.004). In multivariate analysis, IgM retained its independent prognostic value for DFS ( p = 0.048, HR = 0.506, 95% CI = 0.257-0.995). [ABSTRACT FROM AUTHOR]

Conclusions: Nuclear nm23-H1 expression may be useful in identifying elderly patients operated for laryngeal squamous cell carcinoma (LSCC) at higher risk of recurrence. Further studies are needed to clarify the biological role of nm23-H1 in elderly patients with LSCC and to determine how to restore nm23-H1 loss of expression/function. Objectives: Nowadays more than 50% of cancer cases are elderly patients and this percentage is expected to be 70% by 2030. Despite advances in LSCC diagnosis and treatment, patient survival has not improved in the last two decades. Novel, effective strategies should rely also on receptor-mediated LSCC-targeted therapy. nm23-H1 protein is related to the tumor cells' metastatic potential, and low nm23-H1 expression in carcinomas often correlates with a poor prognosis. Methods: Immunohistochemistry and image analysis were used to investigate the prognostic value of nm23-H1 expression and subcellular localization in a series of 54 elderly patients consecutively undergoing primary surgery for LSCC. Results: On univariate analysis, the disease recurrence rate correlated inversely with nuclear nm23-H1 expression ( p = 0.014), and disease-free survival (DFS) was longer in patients whose nuclear nm23-H1 levels were ≥2.0% ( p = 0.022). On multivariate analysis, nuclear nm23-H1 expression (hazard ratio (HR) 2.77, p = 0.022) and N stage (HR 3.49, p = 0.007) were prognostically significant in terms of DFS. [ABSTRACT FROM AUTHOR]

Introduction/background: With the advent of TransOral Robotic Surgery (TORS) the ease of transoral procedures has been dramatically improved. TORS is already established for its feasibility, functional and oncological outcomes for selected lesions of oral cavity, oropharynx and laryngopharynx. This study reports on preliminary results with TransOral UltraSonic Surgery (TOUSS) for oncologic resections of oral cavity, oropharyngeal and supraglottic malignancies.Materials and Methods: Eighteen patients with malignancies of oral cavity, oropharynx and supraglottis underwent TOUSS with simultaneous neck dissection and adjuvant therapy as indicated, from January 2018 to April 2019. Essential equipment included the FK-retractor (Gyrus Medical, Tuttilngen, Germany) for TransOral exposure, the Olympus ENDOEYE Flex 5 mm 2D/10 mm 3D deflecting tip video laparoscopes, and 35 cm long ultrasonic harmonic scalpel (Thunderbeat). Parameters evaluated include tumor staging, mouth opening, TOUSS setup time, TOUSS primary removal time, surgical margins, blood transfusions, tracheostomy, postoperative complications, enteral feeding and resumption of oral diet, duration of hospital stay, and survival outcomes.Results: Eighteen patients underwent complete TransOral UltraSonic Surgery (TOUSS), with simultaneous unilateral or bilateral neck dissection. No procedure was abandoned intraoperatively due to difficulty in extirpation of the tumor. Margins were negative for ten patients (55.6%), close in five (27.8%), and positive in three patients (16.7%). Average TOUSS set-up time was 22.5 min (range, 10-30 min) and average TOUSS primary tumor removal time was 35.3 min (range, 15-60 min). Patients started tolerating oral feeds even in the second post op day (mean 6 days), and transitioning to complete oral feeds with removal of the nasogastric tube was achieved in all (mean, 16 days). The average hospital stay was 7.4 days (range 2-16 days). Secondary hemorrhage occurred in two cases and required an emergency tracheostomy and ligation of lingual artery. Minor cervicopharyngeal fistula occurred in four cases and settled in all with conservative non-surgical treatment. Overall survival at 3 years was 70.5%, and disease-specific survival was 94.4%.Conclusion: TransOral UltraSonic Surgery (TOUSS) is a safe and sound alternative method of endoscopic surgical treatment of oral cavity, oropharynx and supraglottic neoplasms. Advantages of this technique include faster resection time, intraoperative assistance from Narrow Band Imaging, easy affordability compared to TORS, and excellent functional outcomes. [ABSTRACT FROM AUTHOR]

Conclusion: The overexpression of HMGA1 or Ezrin may contribute to the carcinogenesis, development, and metastasis of laryngeal squamous cell carcinoma (LSCC). Objective: To investigate the expression of HMGA1 and Ezrin in LSCC and analyze their clinical significance. Methods: The expression of HMGA1 and Ezrin was analyzed by immunohistochemistry (IHC) in 50 cases of LSCC. Thirty cases of laryngeal polyp and 30 cases of atypical hyperplasia of larynx were studied as controls. The expression of HMGA1 and Ezrin was analyzed by real-time PCR and by Western blot in 30 cases of LSCC; samples from adjacent normal epithelial tissues in 30 cases were studied as controls. Results: (1) IHC revealed that the positive rate of HMGA1 protein was 68.0% (34/50), 53.3% (16/30), and 13. 3% (4/30) in LSCC, atypical hyperplasia of larynx, and laryngeal polyp ( p < 0.05), and the positive rate of Ezrin protein was 64.0% (32/50), 50.0% (15/30), and 23.3% (7/30) ( p < 0.01), respectively. (2) Real-time PCR demonstrated that the mean relative mRNA expression levels of HMGA1 in LSCC and in normal tissues were 2.41 ± 0.40 and 1.05 ± 0.18, respectively ( p < 0.01). The mRNA levels of Ezrin in LSCC and in normal tissues were 1.79 ± 0.27 and 1.04 ± 0.22, respectively ( p < 0.05). (3) Western blotting revealed that the mean relative protein expression levels of HMGA1 in LSCC and in normal tissues were 1.73 ± 0.60 and 0.35 ± 0.17, respectively ( p < 0.01). The protein levels of Ezrin in LSCC and in normal tissues were 1.82 ± 0.77 and 0.42 ± 0.20, respectively ( p < 0.01). [ABSTRACT FROM AUTHOR]

Abstract: Concurrent chemoradiation (CRT) is currently the most effective strategy for organ preservation in locally advanced laryngeal squamous cell carcinoma (SCC) unsuitable for function-preserving surgery. The larynx preservation approach of induction chemotherapy followed by radiotherapy in responders is based on the hypothesis that tumours that show a satisfactory response to induction chemotherapy are more likely to respond to radiation-based treatment. This enables the use of chemotherapy response to identify patients who are more likely to achieve long-term disease control with organ-preserving therapies. An induction chemotherapy response allows prognostication, outcome prediction and treatment selection in patients with locally advanced laryngeal SCC. Excellent survival outcomes have been achieved with induction chemotherapy followed by CRT as definitive therapy in responders. The addition of docetaxel to cisplatin and 5-fluorouracil induction chemotherapy has also resulted in higher larynx preservation rates. Future organ preservation studies should assess whether induction chemotherapy with docetaxel, cisplatin and 5-fluorouracil followed by CRT in responders improves survival compared with an unselected approach of primary CRT in all eligible patients with T2 or T3 laryngeal SCC. The primary end point of such studies should be laryngo-oesophageal dysfunction-free survival, which focuses on the treatment goals of survival, disease control and laryngeal–oesophageal function after therapy. In addition, the inclusion of patients with N2 or N3 disease will help to determine whether the addition of docetaxel, cisplatin and 5-fluorouracil to CRT reduces the incidence of distant relapse in advanced laryngeal SCC. Other areas of interest include the use of concurrent cetuximab in place of platinum-based chemotherapy with radiotherapy in larynx preservation and the search for better predictive markers of successful larynx preservation than induction chemotherapy response. [Copyright &y& Elsevier]

Objective: Tumor-associated tissue eosinophilia (TATE) has been noted in human cancers, sometimes with different results regarding their association with clinical outcome. In this study, the association between TATE and prognostic parameters of supraglottic laryngeal cancer was analyzed. Materials and methods: Sixty-two patients with diagnosis of supraglottic laryngeal squamous cell carcinoma and who treated surgically in our center were evaluated. The cases were divided into 3 categories according to the average number of eosinophils per high-power field (400x): 0 (negative), 1-5 (grade 1+), more than 5 (grade 2+). Results: We found 24 TATE-negative (38.7%) and 38 TATE-positive (61.3%) cases. There was not any statistically significant correlation between TATE and tumor differentiation, vascular invasion, perineural invasion, lymph node metastasis, patients' ages, T stages (p>0.05). As expected, vascular invasion correlated with lymph node metastasis (p=0.001). Conclusion: The results of this study showed that TATE has no correlation with prognostic parameters such as histologic differentiation, vascular invasion, perineural invasion, lymph node metastasis, patients' ages and T stages in supraglottic laryngeal squamous cell carcinoma. The data suggest that stromal eosinophilic infiltration is not useful for determining biological aggressiveness in supraglottic laryngeal cancer. [ABSTRACT FROM AUTHOR]

A clinicopathological analysis of multicentricity in patients treated with either supraglottic horizontal laryngectomy or supracricoid partial laryngectomy for supraglottic squamous cell carcinoma of the larynx was conducted. This study included 63 patients who underwent supracricoid partial laryngectomy or supraglottic horizontal laryngectomy for T2 or T3 supraglottic laryngeal squamous cell carcinoma. The patients were divided into two groups: Group 1 included patients with one focus of the tumor (monocentric), and Group 2 included patients who had more than one focus of the tumor (multicentric) diagnosed after pathology examination. Forty-eight (76.2 %) of the patients had one focus of the tumor (Group 1) and 15 (23.8 %) of the patients had more than one focus of the tumor (Group 2). The rates of lymph node metastasis in Group 1 and Group 2 were 12.5 and 60 %, respectively. The second focus was invasive in seven (46.6 %) of the patients, carcinoma in situ in six (40 %) of the patients, and both invasive and carcinoma in situ in two (13.3 %) patients. The overall 3- and 5-year survival rates of Groups 1 and 2 were 77.1-66.7 % and 56.2-46.7 %, respectively. With regard to survival rates, no statistically significant difference was observed between Group 1 and Group 2 ( p = 0.576). The lack of statistical significance might have been associated with the low sample size. Although multicentric tumors of the supraglottic larynx have high incidence of nodal metastasis, no significant increase in the rate of recurrence was determined. [ABSTRACT FROM AUTHOR]

J Oral Pathol Med (2013) 42: 154-161 Background: BCL2L12 is a recently identified gene belonging to the BCL2 family, members of which are implicated in head and neck squamous cell carcinoma (HNSCC). We have recently shown that BCL2L12 mRNA expression is an unfavorable prognostic indicator in nasopharyngeal carcinoma (NPC) and that BCL2L12 can be regarded as a novel, useful tissue biomarker for the prediction of NPC patients' short-term relapse. The aim of this study was to analyze the mRNA expression of the novel apoptosis-related gene BCL2L12 in patients with HNSCC. Methods: Total RNA was isolated from 53 malignant tumors originating in larynx, pharynx, tongue, buccal mucosa, parotid glands, and nasal cavity, as well as from 34 adjacent non-cancerous tissue specimens, resected from patients with HNSCC. A highly sensitive real-time PCR method for BCL2L12 mRNA quantification in head and neck tissues was developed using the SYBR® Green chemistry. After preparing cDNA by reverse transcription, relative quantification was performed using the comparative CT () method. Results: BCL2L12 mRNA levels were lower in laryngeal tumors of advanced tumor, node, metastasis (TNM) stage or bigger size and in well-differentiated malignant tongue neoplasms, compared with early-stage laryngeal tumors or poorly differentiated tongue tumors. Interestingly, the BCL2L12 expression showed significant discriminatory value, distinguishing efficiently patients with tongue squamous cell carcinoma (SCC) from non-cancerous population. Conclusions: This is the first study examining the BCL2L12 mRNA expression in HNSCC. Our results suggest that BCL2L12 mRNA expression may serve as a potential prognostic biomarker in tongue and/or larynx SCC, which principally constitute the great majority of HNSCC cases worldwide. [ABSTRACT FROM AUTHOR]

Conclusion: Patients who received concurrent chemoradiation therapy or radiation therapy alone were followed over a long term. The complete response (CR), 10-year survival, and 10-year larynx preservation rates were 87.5%, 95.3%, and 75.1%, respectively. Statistically, concurrent chemoradiation therapy contributes to laryngeal preservation but not to the survival rate. Objective: To determine the additive and synergistic effects of anticancer chemotherapy combined with chemoradiation therapy for squamous cell carcinoma (SCC) of the glottic larynx. Methods: Eighty-nine patients with untreated T2N0M0 SCC of the glottic larynx were included. Thirty-two patients received treatment cycles consisting of intravenous cisplatin (CDDP) on day 1 (80 mg/m2) and intravenous 5-fluorouracil (5-FU) over 120 h on days 2-6 (600 mg/m2/day) every 4 weeks. Radiotherapy was delivered by a 4 MV linac X-ray machine at a dose of 66 Gy. Fifty-seven patients received radiotherapy alone. Results: After chemoradiation therapy, the overall response, CR, 10-year survival, and 10-year larynx preservation rates were 100%, 87.5%, 95.3%, and 75.1%, respectively. Side effects included leukopenia, neutropenia, mucositis, and dermatitis. Seven patients (21.9%) required salvage surgery. Pathological findings confirmed that the treatment regimen caused marked cancer tissue degeneration. Histologic examination of surgical specimens suggested that the safety margin for partial laryngectomy was 4 mm from the gross tumor. [ABSTRACT FROM AUTHOR]

Conclusion: Concurrent chemoradiation therapy with docetaxel (DOC) at a dose of 10 mg/m2 twice a week contributed to laryngeal preservation. Objective: To determine laryngeal preservation following concurrent chemoradiation therapy with DOC. Methods: A total of 141 patients with untreated T2N0M0 squamous cell carcinoma of the glottic larynx were included in the study. The treatments were either radiation therapy alone or DOC intravenously administered at a dose of 10 mg/m2 once or twice a week during radiotherapy with 4 MV linac X-ray (total of 66 Gy for 33 days). Results: The response and CR rates were 100% and 90.5% in the once-weekly combination group, and 100% and 97.6% in the twice-weekly combination group, respectively. The 5-year survival rates were 76.8% in the once-weekly combination group and 96.8% in the twice-weekly combination group. The 5-year laryngeal preservation rates were 83.8% in the once-weekly combination group and 97.6% in the twice-weekly combination group. The most common side effects were mucositis, dermatitis, and alopecia. The patients who received DOC twice a week showed more severe cancer tissue degeneration, and pathological examination of serial sections indicated that the safety margin for partial laryngectomy was considered to be 3 mm from the gross tumor with good glottal closure. [ABSTRACT FROM AUTHOR]

Abstract: Aims: To evaluate the prognostic significance of potential tumour markers of hypoxia and apoptosis in early squamous cell carcinoma of the glottic larynx managed with radiotherapy. Materials and methods: In total, 382 patients with T1 and T2 squamous cell carcinoma of the glottic larynx (vocal cords) received radical radiotherapy (50–55 Gy, in 16 fractions in 98% of cases). Pre-treatment haemoglobin was available for 328 patients; biopsy samples were available for 286. Immunohistochemistry was carried out for carbonic anhydrase-9 (CA-9), hypoxia inducible factor-1α (HIF-1α) and Bcl-2. Results: At 5 years, locoregional control was achieved in 88.2%, cancer-specific survival in 95.0% and overall survival in 78.7%. Adverse prognostic factors for locoregional tumour recurrence were pre-treatment haemoglobin <13.0 g/dl (P = 0.035, Log rank test; sensitivity 0.28, specificity 0.84) and stage T2 rather than T1 (P = 0.002). The effect of haemoglobin level on locoregional control was not significant when stratified by the median of 14.2 g/dl (P = 0.43) or as a continuous variable (P = 0.59). High CA-9 (P = 0.11), HIF-1α (P = 0.67) and Bcl-2 (P = 0.77) expression had no prognostic significance. Conclusions: High CA-9, HIF-1α and Bcl-2 do not add to the prognostic significance of tumour stage and lower haemoglobin in predicting failure of local control in early glottic larynx squamous cell carcinoma managed with radiotherapy. The effect of haemoglobin was not strong enough to be useful as a prognostic biomarker. [Copyright &y& Elsevier]

Objectives: The aim of this study was to determine the frequency and genotype of human papillomavirus (HPV) infections in head and neck squamous cell carcinomas (HNSCCs) and benign head and neck tumours. Methodology: A retrospective study was performed on 150 samples of patients diagnosed with HNSCCs and 50 samples obtained from patients diagnosed with benign head and neck tumours. Tumour DNA was amplified using polymerase chain reaction (PCR) with HPV consensus and multiplex primers. Results: Six of the 150 (4%) HNSCCs were HPV positive. HPV16 was the most prevalent type, with single infections present in 3/6 (50%) cases, whereas HPV18 and HPV33 were detected in 2/6 (33%) and 1/6 (17%), respectively. HPV infections were detected in 3 (50%) cases of oral cavity and 3 (50%) cases of pharynx. Conclusions: There was a significant association between HPV infection and HNSCCs (P < 0.05). The present data support the importance of HPV infection in oral and larynx tumours. [ABSTRACT FROM AUTHOR]

Objective:This study aimed to investigate the relationship between focal adhesion kinase expression and clinicopathological factors, cell apoptosis and proliferation, and overall survival, in laryngeal squamous cell carcinoma.Methods:Immunohistochemical staining was used to detect the expression of focal adhesion kinase and proliferating cell nuclear antigen in tissue samples. Apoptotic cells were assessed using the terminal deoxynucleotidyl transferase mediated deoxyuridine triphosphate nick end labelling (‘TUNEL’) method.Results:The proportion of focal adhesion kinase expression was 73.26 per cent in tumour tissues, significantly greater than in normal tissues (p < 0.05), and was significantly related to laryngeal cancer clinical stage, lymph node metastasis and overall survival (p < 0.05). In the tumour cases assessed, up-regulation of focal adhesion kinase expression was significantly associated with decreased cell apoptosis and increased proliferation (p < 0.05).Conclusion:These findings suggest that focal adhesion kinase may affect laryngeal squamous cell carcinoma progression through regulation of cell apoptosis and proliferation. Focal adhesion kinase expression is a major prognostic factor in laryngeal cancer patients. [ABSTRACT FROM PUBLISHER]

Objectives: Radiation Therapy Oncology Group study 91-11 found that in resectable advanced laryngeal cancer, the locoregional control rate achieved with reduced intra-arterial cisplatin and concurrent radiotherapy (RADPLAT) was comparable to that of a concurrent chemoradiotherapy arm, with reduced toxicities. However, distant metastases were more frequent. Our study retrospectively evaluated the efficacy and feasibility of adjuvant chemotherapy with S-1, an oral fluoropyrimidine, for distant metastases following reduced RADPLAT. Methods: We analyzed 61 patients who were treated with reduced RADPLAT and achieved a complete response at the primary site. After the use of reduced RADPLAT, 24 patients were administered S-1 for 2 weeks followed by 1 week of rest, and the cycle was repeated for 6 months (S-1+ group). Thirty-seven patients were not administered S-1 (S-1-group). Results: The hazard ratio for distant metastases in the S-1+ group was 0.114 (95% confidence interval, 0.015 to 0.881; p = 0.0374). There was a significant difference in disease-free survival in favor of the S-1+ group (p = 0.0455). Nineteen patients (79.2%) in the S-1+ group received S-1 according to the planned schedule and dose. Grade 3 toxicities were observed in 2 patients (8.3%), but there was no grade 4 event. Conclusions: In resectable advanced laryngeal cancer, S-1 adjuvant chemotherapy is an effective and feasible treatment option to control distant metastases following reduced RADPLAT. [ABSTRACT FROM AUTHOR]

Imaging plays an important complementary role to clinical examination and endoscopic biopsy in the evaluation of laryngeal cancers. A vast majority of these cancers are squamous cell carcinomas (SCC). Cross.sectional imaging with contrast-enhanced computed tomography (CT) and magnetic resonance (MR) imaging allows excellent depiction of the intricate anatomy of the larynx and the characteristic patterns of submucosal tumor extension. CT, MRI and more recently PET.CT, also provide vital information about the status of cervical nodal disease, systemic metastases and any synchronous malignancies. Additionally, certain imaging-based parameters like tumor volume and cartilaginous abnormalities have been used to predict the success of primary radiotherapy or surgery in these patients. Integration of radiological findings with endoscopic evaluation greatly improves the pretherapeutic staging accuracy of laryngeal cancers, and significantly impacts the choice of management strategies in these patients. Imaging studies also help in the post-therapeutic surveillance and follow-up of patients with laryngeal cancers. In this article, we review the currently used laryngeal imaging techniques and protocols, the key anatomic structures relevant to tumor spread and the characteristic patterns of submucosal extension and invasion of laryngeal cancer. The role of CT, MRI and PET-CT in the evaluation of patients with laryngeal SCC and the impact of imaging findings on prognosis and clinical management is also discussed. [ABSTRACT FROM AUTHOR]

Objective:We present the first reported case of a paraganglioma of the larynx occurring concurrently with squamous cell carcinoma in an irradiated neck.Method:We present a case report and a literature review of paraganglioma of the larynx.Case report:A 78-year-old woman was found to have a mass on the laryngeal surface of the epiglottis and non-functioning larynx, four months after radical radiotherapy for biopsy-proven squamous cell carcinoma. Repeated positron emission tomography computed tomography was highly suggestive of residual malignancy. Given these findings, and the fact that the patient was aspirating, she was treated with total laryngectomy, and was found to have a paraganglioma of the larynx.Conclusion:This is the first report of such a case. Its importance is three-fold in that it demonstrates: the coexistence of paraganglioma and squamous cell carcinoma; the difficulties that can be encountered in the diagnosis; and the use of radiotherapy in the treatment of paraganglioma. [ABSTRACT FROM PUBLISHER]

Angiogenesis is a hallmark of cancer, fundamental to its growth. The 'angiogenic switch' occurs when pro-angiogenic factors are not balanced by anti-angiogenic factors. A correlation between angiogenic properties and oncological prognosis (for laryngeal squamous cell carcinoma (LSCC) too) was first hypothesized in the 1990s. An exhaustive literature review was performed to investigate available data on angiogenesis markers and their biological role and therapeutic potential in LSCC. The prognostic significance of microvascular density in LSCC was investigated with endothelial targets, e.g. CD105, CD34, and CD31. Epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF), VEGF receptor 2, angiogenin, hypoxia-inducible factor 1, and other biological markers were also studied. Only anti-EGFR therapy has been approved by the USFood and Drug Administration (FDA) for head and neck carcinoma in recent years, while several agents interfering with VEGF and its receptors are being studied. Experimental findings indicate that anti-CD105 monoclonal antibodies efficiently inhibit tumor angiogenesis. There are two main ways to approach the vascular profile of solid malignancies: by inhibiting new vessel formation (anti-angiogenic therapy) or selectively damaging neoplastic vessels (vascular targeting therapy). In advanced LSCC, both these strategies seem promising and warrant further preclinical and clinical investigation. [ABSTRACT FROM AUTHOR]

Conclusion: A long-term study was carried out on 57 patients treated with radiation alone who had T2N0M0 squamous cell carcinoma of the glottic larynx. The response and survival rates were satisfactory, but the complete response (CR) and the larynx preservation rates showed a need for improvement. Thirty-four patients underwent salvage operations and a safe margin for the partial laryngectomy was evaluated by histopathological examination of serial sections of the surgical specimen. Objective: Although the effectiveness of combined chemoradiation therapy in the treatment of head and neck cancer has been reported, the facts remain unclear. The purpose of this study was to analyze the long-term outcomes of radiation therapy alone for T2N0M0 squamous cell carcinoma of the glottic larynx, i.e. the survival rate, the larynx preservation rate, and the reality of salvage operations. This is expected to contribute to an understanding of the synergistic effects of anticancer drugs used in combined chemoradiation therapy, the use of which will be expanded in the future. The reason for this is that the radiation source, radiation field, and radiation dose are nearly identical for patients with T2N0M0 squamous cell carcinoma of the glottic larynx. Methods: The subjects were 57 patients with untreated T2N0M0 squamous cell carcinoma of the glottic larynx. There were 55 males and 2 females. Their ages ranged from 31 to 86 years. The 4 MV Liniac X-ray external beam radiation therapy was carried out via two-dimensional horizontal opposing ports, 2 Gy per dose, five times a week with a total of 66 Gy. Results: In 57 patients, we observed CR in 33 patients, partial response (PR) in 20 patients, no change (NC) in 4 patients, and progression disease (PD) in none of the patients. The response rate was 93.0% and the CR rate was 57.9%. The survival rates (Kaplan-Meier method) were: 5-year survival rate of 88.5% and 10-year survival rate of 73.5%. The larynx preservation rates (Kaplan-Meier method) were: 5-year larynx preservation rate of 60.4% and 10-year larynx preservation rate of 50.1%. The main side effect of grade 3 or more was only stomatitis in four patients, all of which were reversible changes (CTCAT v3.0 JCOG/JSCO). Salvage operation was required in 34 (59.6%) of 57 patients, 10 patients underwent partial laryngectomy, total laryngectomy was performed in 3 of the 10 patients following the partial laryngectomy, and 27 patients (47.4%) underwent total laryngectomy. The surgical specimens were serially sectioned at a thickness of 4 μm and examined histopathologically and compared to the macroscopic findings at surgery. The safe margin for partial laryngectomy was considered grossly to be 5 mm from the edge of the tumor. [ABSTRACT FROM AUTHOR]

Background: Early-stage laryngeal squamous cell carcinoma is managed with radiotherapy or endoscopic surgery. Although curerates are high, radiation failures often require total laryngectomy for salvage. Biomarkers that can predict tumour radioresistancemay be useful in modifying the treatment approach for individual patients. Methods: Retrospective patient chart review yielded 75 patients with T1-T2 glottic squamous cell carcinoma treated with radiation therapy at the London Health Sciences Centre. Pretreatment tumour biopsies were immunostained for B-cell lymphoma 2 (Bcl-2), Ki-67, and epidermal growth factor receptor (EGFR) to correlate biomarker expression with disease-freesurvival (DFS). Results: Ki-67 expression was strongly associated with recurrence following radiation and independently predicted poor DFS(hazard ratio 4.86, 95% CI 1.58-15.00; p = .006). EGFR and Bcl-2 were not associated with a risk of recurrence. Conclusions: Ki-67 expression identified a subset of patients with increased risk of local recurrence after radiation therapy. Ki-67 expression can potentially guide improved personalized treatments for patients with early-stage glottic squamous cellcarcinomas. [ABSTRACT FROM AUTHOR]

We report herein a rare case of typical carcinoid occurring primarily in the epiglottis. The patient was a 70-year-old man. On initial examination, a polypoid lesion with irregular surface near the center right-hand side of the laryngeal surface of the epiglottis was observed, and a biopsy was performed. Pathological examination of the specimen suggested the possibility of adenocarcinoma. Surgical excision was performed by means of laryngomicrosurgery. A Weerda-type laryngoscope was used to open the larynx, supplemented by rigid nasal sinus surgery endoscopes, and the right-hand half of the epiglottis were excised was ensured using a CO2 laser. Postoperative pathological diagnosis was negative for adenocarcinoma and squamous cell cancer; typical carcinoid was diagnosed according to the World Health Organization criteria. Aspiration occurred postoperatively, swallowing training was therefore provided, and the patient was discharged from hospital 2 months after surgery when he was able to eat normally. As of 4 years after surgery, the patient remains under follow-up observation by means of PET-CT and neck, thoracic, and abdominal CT administered at appropriate intervals, but no findings indicating obvious recurrence or metastasis have been observed, and the patient displays good swallowing function. [ABSTRACT FROM AUTHOR]

Squamous cell carcinoma (SCC) involving the larynx in childhood is very rare, especially in the ages younger than 10 years. Most of the reported cases are transformed from the recurrent respiratory papillomatosis (RRP) with human papilloma virus (HPV) infection. Due to the RRP long course, the rarity and the unspecific symptoms of the cancer, they usually are diagnosed at late stages. Controversy exists regarding the causes and the treatments of these kinds of diseases. Here, we reviewed the related reports and presented a case of 7-year-old boy who had an advanced well-differentiated SCC of the larynx which transformed from RRP with HPV genotyping test negative. The patient underwent only the resection of involved tissues and no other treatments. Except for hoarseness in his voice, the boy is going well and has had an uneventful course of 10 years following operative treatment. [ABSTRACT FROM AUTHOR]

Thirteen laryngeal squamous cell carcinoma cell lines were recently studied by array comparative genomic hybridization (array-CGH) in order to identify recurrent DNA copy number alterations in the tumor genome. A highly amplified region 22q11.2 was found in two of the thirteen cell lines. Two established oncogenes CRKL and MAPK1 are localized in this region, but only CRKL was amplified in both cell lines. Therefore, to check if amplification of either CRKL or MAPK1 genes may be important in the pathogenesis of laryngeal squamous cell carcinoma, the DNA copy number and mRNA expression were measured in a cohort of 17 LSCC cell lines by quantitative real-time PCR (qPCR). For the CRKL gene gains of the copy number were found in 3/17 cell lines, while overexpression was found in 6/17 cell lines. Gains in the copy number for the MAPK1 gene were found in 1/17 cell lines, but overexpression was not detected in any cell line. A highly significant correlation between DNA copy number and expression for CRKL gene, but not for MAPK1 gene was established using the Pearson test. Thereafter, 46 primary samples of laryngeal cancer were tested by qPCR to check for possible gains in copy number of the CRKL gene. Gains were found in 3/46 cases. These results suggest that CRKL, but not MAPK1 is the target oncogene of the rare but recurrent amplification at 22q11.2 in laryngeal squamous cell carcinoma. [ABSTRACT FROM AUTHOR]

Background: Primary radiotherapy (RT) is a mainstay of treatment for laryngeal squamous cell carcinoma (LSCC). Although the cure rates for early (T1) vocal cord tumours are high, RT proves ineffective in up to a third of T3 carcinomas. Moreover, RT is associated with debilitating early- and late-treatment-related toxicity, thus finding means to de-escalate therapy, while retaining/augmenting therapeutic effectiveness, is highly desirable. p53 is a key mediator of radiation responses; we therefore investigated whether Nutlin-3, a small-molecule inhibitor of MDM2 (mouse double minute 2; an essential negative regulator of p53), might radiosensitise LSCC cells.Methods: We performed clonogenic assays to measure radiosensitivity in a panel of LSCC cell lines (for which we determined p53 mutational status) in the presence and absence of Nutlin-3.Results: LSCC cells harbouring wild-type p53 were significantly radiosensitised by Nutlin-3 (P<0.0001; log-rank scale), and displayed increased cell cycle arrest and significantly increased senescence (P<0.001) in the absence of increased apoptosis; thus, our data suggest that senescence may mediate this increased radiosensitivity.Conclusion: This is the first study showing Nutlin-3 as an effective radiosensitiser in LSCC cells that retain wild-type p53. The clinical application of Nutlin-3 might improve local recurrence rates or allow treatment de-escalation in these patients. [ABSTRACT FROM AUTHOR]

Background:Spontaneous regression of solid malignancy is extremely rare. It is virtually unheard of in the last half century in the published literature. The overwhelming majority of medical professionals do not know that this phenomenon exists.Case report:This paper reports such a case involving a patient with proven laryngeal squamous cell carcinoma in New Zealand. Whilst waiting for definitive treatment, he was afflicted with prolonged septicaemia secondary to peritonitis from percutaneous endoscopic gastrostomy tube insertion. Following a total laryngectomy, histology of the specimen did not contain any evidence of neoplasia.Conclusion:Based predominantly on work established by Dr William Coley, we believe that a period of prolonged pyrexia preceding definitive surgery contributed to this apparent ‘miracle’. The time may be ripe to further debate on whether the medical profession should consider pyrexia therapy as a last resort treatment for patients deemed incurable by conventional methods. [ABSTRACT FROM PUBLISHER]

Background:The term “collision tumor” refers to the coexistence of two histologically distinct malignant tumors within the same mass. Collision tumors involving the thyroid gland and/or neck region are especially uncommon, with most reported cases involving papillary thyroid carcinoma in coexistence with medullary thyroid carcinoma, follicular carcinoma, and metastatic disease, the latter including a rare occurrence of metastatic liposarcoma and thyroid papillary carcinoma. A collision tumor of papillary thyroid carcinoma and squamous cell carcinoma primary to the thyroid has also been reported.Summary:We now report a collision tumor comprised of well-differentiated papillary thyroid carcinoma and squamous cell carcinoma that originated as a laryngeal primary tumor. Histologically, the thyroid mass is consisted of well-differentiated papillary thyroid carcinoma. The laryngeal mass consisted of in situand invasive squamous cell carcinoma. Both cancers were extensively infiltrative into the soft tissues of the neck and paraglottic space where the histologically distinct tumor types approximated one another but were not admixed with each other. Additionally, cervical lymph nodes showed metastatic carcinoma, including independent cervical lymph nodes with metastatic squamous cell carcinoma only, cervical lymph nodes with metastatic papillary thyroid carcinoma only, and cervical lymph nodes with foci of both papillary thyroid carcinoma and squamous cell carcinoma.Conclusion:As best we can determine this is the first publication of a collision tumor comprised of a well-differentiated papillary thyroid carcinoma and squamous cell carcinoma that originated as a laryngeal primary tumor. For any patient with a thyroid mass that appears to be in continuity with a laryngeal mass, more commonly one would find invasive thyroid cancer, but one must consider a collision tumor in the differential diagnosis. [ABSTRACT FROM AUTHOR]

Simple Summary: Anti-PD-1 immunotherapies are approved for head and neck squamous cell carcinoma in the recurrent/metastatic setting, and utilization of these high-cost biologics is expected to increase as other indications are approved. Due to the high cost and selective response rate of these immunotherapy biologics in HNSCC, it is imperative to better define which patient subsets will realize a clinically meaningful benefit with anti-PD-1 treatment. The impact of anatomical site and p16 status on the efficacy of anti-PD-1 inhibitors remains unresolved. We showed that anatomical site and p16 status are associated with overall survival in anti-PD-1-treated HNSCC patients from a single-institution, real-world cohort. In head and neck squamous cell carcinoma (HNSCC), anti-PD-1 inhibitors are approved for recurrent/metastatic (R/M) disease and anticipated to expand to other indications. The impact of p16 status and anatomical site on overall survival (OS) in immunotherapy-treated HNSCC patients remains unresolved. We performed a retrospective analysis of R/M HNSCC patients receiving anti-PD-1 immunotherapy at our academic medical center with an extensive community satellite network. Fifty-three R/M HNSCC patients were treated with anti-PD-1 immunotherapy and had a median OS of 6 months. Anatomical site was associated with distinct OS; oropharynx and larynx patients have superior OS compared to oral cavity patients. Analysis of the OPSCC subset showed p16+ status as a favorable, independent prognostic biomarker (HR 7.67 (1.23–47.8); p = 0.029). Further studies to assess the link between anatomical site, p16 status, and anti-PD-1 treatment outcomes in large cohorts of R/M HNSCC patients managed in real-world clinical practices and clinical trials should be prioritized. [ABSTRACT FROM AUTHOR]

Laryngeal squamous cell carcinoma (LSCC) is one of the most common laryngeal tumors, and its incidence is increasing yearly; however, whether lymph node dissection should be performed during surgery remains unclear. We retrospectively analyzed the clinical and pathological data of 246 cases of LSCC and developed a nomogram for the prediction of lymph node metastasis (LNM) of LSCC. The predictive performance and consistency of the model were evaluated using the consistency coefficient (C-index) and calibration curve, respectively. Among 246 cases of LSCC, 52 cases had metastasis with a positivity rate of 21.14%. Multivariate analyses showed that dysphagia, clinical T stage, and pathological differentiation were independent risk factors for LNM in LSCC. The accuracy of the contour map used to predict the risk for LNM was 0.809. Overall, this nomogram model can be used to evaluate LNM in patients with LSCC before surgery to decide whether to conduct neck dissection and improve patient prognosis. [ABSTRACT FROM AUTHOR]