Perceptual, aerodynamic and acoustic outcomes of surgical technique for sulcus vocalis patients: A systematic review and meta analysis.

BACKGROUND: Sulcus Vocalis (SV) is a voice disorder characterized by the parallel invagination of the vocal fold epithelium that adheres to the vocal ligament. This condition disrupts the vibratory function, leading to glottal incompetence, hoarseness, and vocal impairment. Despite various proposed surgical techniques, a standardized treatment approach remains elusive. METHODS: We conducted a comprehensive search across PubMed/Medline, Embase, Web of Science, Scholar, and the Cochrane Library for studies on SV treatment. The inclusion criteria comprised original studies comparing pre- and post-treatment vocal outcomes in SV patients, published in English. We excluded case reports, reviews, studies without continuous data, and patients with vocal scar/atrophy. RESULTS: Fifteen observational studies were included (361 patients, 53.73 % male, average age 41.64 years). 80 % of these studies employed self-reported outcomes, while 81.25 % analyzed acoustic/aerodynamic data. The follow-up period varied from 4 to 44 months. All techniques significantly improved Voice Handicap Index (VHI) scores (p < 0.001). Dissective and combined techniques exhibited greater reductions in VHI-30/10 (p < 0.001). Maximum Phonation Time (MPT) improved significantly across all techniques (p < 0.001), with dissective techniques demonstrating superior MPT outcomes (p < 0.001). Jitter improved significantly for dissective and injective techniques (p < 0.001), as did Shimmer for all techniques (p < 0.001). Notably, combined techniques displayed the most significant reductions (p < 0.001). CONCLUSIONS: Surgical treatments significantly improve subjective, aerodynamic, and acoustic outcomes in SV patients. Dissective and combined dissective/injective techniques appear to yield better perceptual and phonatory outcomes compared to injective techniques alone. Further research is necessary to establish the optimal treatment approach for SV.

Isoprognostic functional CT map for open partial horizontal laryngectomy.

PURPOSE: To identify a radiological map of laryngeal subsites whose involvement by the tumor could predict patients' functional outcomes after open partial horizontal laryngectomy (OPHL). METHODS: The present retrospective analysis concerned 96 patients with glottic squamous cell carcinoma, who were radiologically staged with contrast-enhanced neck CT scans before undergoing supracricoid or supratracheal laryngectomy. A radiological map of patients' functional risk was developed by considering the distribution of functional outcomes in relation to the laryngeal subsites involved. The functional outcomes considered were: (i) decannulation at discharge; (ii) time to removal of the nasogastric feeding tube (NFT); (iii) postoperative complication rate; and (iv) length of hospital stay. RESULTS: Involvement of the anterior supraglottis was related to a longer need for NFT, and a longer hospital stay (p = 0.003, and p = 0.003, respectively). Involvement of the posterior glottis negatively affected the time to decannulation, and the likelihood of postoperative complications (p = 0.000, and p = 0.002, respectively). CONCLUSIONS: Anterior glottic small tumors (without significant subglottic and/or supraglottic extension) are related to the best functional outcomes after OPHL, since the suprahyoid epiglottis and both the arytenoids are likely to be spared.

The role of central neck dissection and adjuvant treatment in pT4aN0 laryngeal carcinoma treated with open partial horizontal laryngectomy.

PURPOSE: The study aimed to identify parameters that could predict oncological and functional outcomes in patients with pT4aN0 laryngeal squamous cell carcinoma (LSCC) who underwent open partial horizontal laryngectomy (OPHL). The role of paratracheal neck dissection (PTND) was analyzed as the primary outcome. Additionally, the study compared the outcomes of patients who underwent postoperative radio/chemotherapy (PORT/PORCT) with those who refused or did not adhere to adjuvant treatments. METHODS: Twenty-nine OPHL patients whose pathological exam was consistent with pT4aN0-x disease were enrolled and their clinical charts were retrospectively reviewed. The study analyzed oncological outcomes, such as local, regional, and distant recurrence rates (RR), overall survival (OS), disease-free survival (DFS), and disease-specific survival (DSS). Additionally, functional results were analyzed, including decannulation rate, hospitalization time, and postoperative complication rate. RESULTS: The study revealed and overall recurrence rate of 27%. The final rates for OS and DSS were 68% and 79%, respectively. Based on the univariate analysis the PTND was significantly associated with longer DFS. No significant differences inoncological outcomes were observed between pT4a patients who underwent adjuvant radio/radiochemotherapy and those who did not, in terms of RR, DFS, DSS or OS. However, adjuvant treatment was found to significantly increase decannulation time. CONCLUSIONS: In a properly super-selected subgroup of patients with pT4aN0 LSCC, OPHL may beconsidered as a conservative surgical option even without adjuvant treatment. However, for optimal oncological outcomes, it is strongly recommended to consider a central compartment dissection in cases of hypoglottic and anterior extra-laryngeal tumor extension.

The glottic-subglottic laryngectomy: Surgical technique, oncological, and functional outcomes.

OBJECTIVES: The aim of this article was to describe the surgical technique and report the oncological and functional outcomes of the partial glottic-subglottic laryngectomy (GSL). METHODS: A retrospective review of the clinical charts of patients who underwent GSL for laryngeal cancer from 1989 to 2020 at the Otolaryngology Unit of the Vittorio Veneto Hospital, a referral center for laryngeal cancer treatment. RESULTS: The present article considered 36 patients who were submitted to GSL for laryngeal cancer. The pathological exam found squamous cell carcinoma (SCC) in 16 cases, adenoid-cystic carcinoma (ACC) in 9 cases, laryngeal chondrosarcoma in 8 cases, 1 giant cell carcinoma, 1 carcinosarcoma, and 1 metastasis of colon adenocarcinoma. Considering the 16 SCC cases we observed a recurrence rate of 31%, the overall survival (OS) and disease-specific survival (DSS) were 75%. The 9 ACC cases had a recurrence rate of 23% and OS/DSS of 88%. In the 8 chondrosarcomas no relapses were reported and the OS/DSS were 100%. Among the patients without recurrence of the disease, a definitive decannulation was achieved in 21 cases (75%). CONCLUSIONS: The GSL represents a valid alternative to total laryngectomy in selected cases of laryngeal cancer involving the glottic and subglottic regions.

Laryngeal adenoid cystic carcinoma: Radical or conservative surgery?

PURPOSE: The present paper describes our experience in surgical treatment of laryngeal ACC, and discuss the effectiveness of conservative surgery. METHODS: We retrospectively reviewed the clinical charts of 17 patients with laryngeal ACC treated surgically at the Otolaryngology Unit of Vittorio Veneto Hospital (Italy) from November 1989 to April 2020. RESULTS: Fourteen patients underwent partial laryngectomy, and three had a total laryngectomy. Five patients (29%) experienced a laryngeal ACC relapse after a disease-free survival of 66.6 ± 50.1 months. The distant metastasis rate was 17%. At latest follow-up, two patients had died of distant metastatic disease after 156 and 243 months. CONCLUSIONS: Radical surgery for laryngeal ACC does not warrant free margins and even cases with positive deep margins rarely experience any relapsing disease. We recommend that surgical treatment for laryngeal ACC be as conservative as possible.

Video-nystagmographic evidence in more than 700 consecutive cases of road traffic whiplash injury.

PURPOSE: Whiplash injury is a frequent traumatic lesion occurring mainly in road accidents, which may also cause dizziness severe enough to impact everyday life. Vestibular examination is routinely performed on these patients, although the role of the neuro-otologist is still not clearly defined. The main endpoint of this study was to describe the videonystagmography (VNG) evidence in a large cohort of patients who underwent road traffic whiplash injury. METHODS: 717 consecutive patients who reported whiplash-associated disorders due to a road traffic accident underwent clinical examination and VNG. RESULTS: Patients with saccadic test latency anomalies more frequently complained of vertigo, nausea and cochlear symptoms after trauma (p = 0.031, 0.028 and 0.006), while patients with bilateral vestibular weakness at caloric stimulation more often displayed neck pain after trauma (p = 0.005). Patients complaining of positional or cochlear symptoms or with accuracy anomalies at the saccadic test were significantly older than those with no positional, no cochlear symptoms and without accuracy anomalies (p = 0.022, p = 0.034 and p = 0.001). Patients with bilateral vestibular hypofunction were significantly younger (p < 0.001). CONCLUSIONS: VNG evidence, particularly vestibular function and saccadic tests, may be related to damage in the cervical region due to whiplash trauma. These findings suggest that neuro-otologic examination may play a role in properly identifying those who suffer damage caused by whiplash trauma, and in characterizing the severity and prognosis of whiplash-associated disorders.

Two-stage CO2-laser-assisted bilateral cordectomy for cT1b glottic carcinoma.

PURPOSE: The aim of the present paper was to investigate the oncological safety of two-stage bilateral cordectomy for the treatment of cT1b glottic SCC, and to compare its oncological outcome and synechia development rate with those of single-stage procedures. MATERIALS AND METHODS: A retrospective cohort study was performed at the Otolaryngology Unit of Vittorio Veneto Laryngeal Cancer Center (Italy). The prognostic significance of clinical, pathological and surgical factors was also investigated, in terms of recurrence rate and disease-free survival, in a univariate statistical setting. RESULTS: Our results indicate that patients treated with primary two-stage bilateral cordectomy achieved local control in 96% of cases, with 95% disease-specific and 88% overall survival rates, and a 95% organ preservation rate, with anterior synechiae developing in 1 case. Involvement of the deep surgical margins correlated with a worse prognosis. Patients developed anterior synechiae less frequently after two-stage bilateral cordectomy, and experienced no higher recurrence rate or shorter disease-free survival than patients treated with a single-stage procedure. CONCLUSIONS: Two-stage bilateral cordectomy is a safe and effective procedure. In selected patients it could be considered the primary approach for the treatment of early glottic cT1b carcinomas.

Lateral pharyngotomy approach in the treatment of oropharyngeal carcinoma.

Surgery for early-intermediate oropharyngeal squamous cell carcinoma (OPSCC) may involve using transoral endoscopic approaches or open surgical procedures. "Lateral pharyngotomy" (LP) is an open surgical approach that improves exposure of the oropharyngeal region, while avoiding mandibulotomy. The aim of the present study was to retrospectively analyze our experience with the surgical treatment of early-intermediate OPSCC using the LP approach, and to investigate the potentially prognostic clinical and/or pathological factors that might identify patients at higher risk of recurrence after primary surgery. Sixty-four patients with previously untreated early-intermediate (pT1-T2-T3) OPSCC consecutively underwent partial pharyngectomy using a LP approach, performed by the same surgical team at a tertiary head and neck oncology center (Otolaryngology Unit, Vittorio Veneto Hospital, Italy). The 2-year disease-specific survival rates were 86% for stage I-II and 77% for stage III-IV disease. All patients who experienced locoregional or distant metastases died of their disease, while no patients died of any complications of the treatment. Postoperative complications occurred in 25 patients (39%), the most common being pharyngocutaneous fistula. All but one of the patients experienced a complete recovery of oral food intake. In conclusion, the LP approach to oropharyngeal cancer could be a valid open surgical alternative to oropharyngectomy with mandibulotomy for: (a) patients with early-intermediate OPSCC in whom oropharyngeal exposure proves difficult, and/or who are not eligible for transoral endoscopic surgery; (b) HPV-negative OPSCCs; and

Open partial horizontal laryngectomy for salvage after failure of CO2 laser-assisted surgery for glottic carcinoma.

Total laryngectomy (TL) is often still recommended as a salvage approach for recurrent laryngeal squamous cell carcinoma (LSCC). Considering LSCC recurrences after the failure of primary transoral laser microsurgery (TLM), open partial horizontal laryngectomy (OPHL) could be a valid alternative to TL in selected patients. The aim of the present study was to analyze retrospectively the oncological outcome of a consecutive series of 17 patients treated at the Otolaryngology Unit of Vittorio Veneto Hospital (Italy) with OPHL after primary TLM had failed. Nine patients (53 %) had no further recurrences after salvage OPHL. Eight patients had a second recurrence of LSCC after OPHL, and five of them were cured by further salvage treatment, while the other three died of their disease. We found an overall and disease-specific survival both of 82 % and a loco-regional control rate and an ultimate organ preservation rate of 82 and 70 %, respectively. Patients who underwent two-stage bilateral cordectomy for primary glottic carcinoma showed a trend towards a higher rate of second recurrences, a lower ultimate organ preservation rate and a shorter disease-free survival after salvage OPHL. Further studies on larger cohorts of patients are needed to identify potential clinical and/or pathological prognostic parameters capable of pinpointing patients at higher risk of second recurrences after salvage OPHL in cases where TLM has failed. A salvage TL might be reasonably proposed as a first salvage choice in such cases.

Postoperative radiotherapy for laryngeal carcinoma: the prognostic role of subcellular Maspin expression.

PURPOSE: Reported outcomes of postoperative radiotherapy (PORT) for laryngeal squamous cell carcinoma (LSCC) have varied and sometimes been disappointing. The aim of the present preliminary study was to investigate whether a given immunohistochemical pattern of Maspin expression in laryngeal carcinoma cells could be prognostically associated with response to PORT. MATERIALS AND METHODS: Thirty-two consecutive patients treated for LSCC with primary surgery and PORT. The subcellular (nuclear vs non-nuclear) pattern of Maspin expression was assessed immunohistochemically on LSCC surgical specimens and analyzed in relation to recurrence rate (RR) and disease-free survival (DFS). RESULTS: A non-nuclear Maspin expression was found in 23 of 32 cases (72%), and all recurrences (17 cases) occurred in this subgroup of patients. A non-nuclear Maspin expression was strongly associated with recurrence [p = 0.0002, hazard ratio (HR) 5.58] and a shorter DFS (p = 0.0004) after PORT for LSCC. Even in N0 patients, a non-nuclear Maspin expression was associated with a significantly higher RR (p = 0.04, HR 1.42) and a shorter DFS (p = 0.02). Among the common clinic-pathological parameters considered, only N stage showed a trend toward an association with prognosis in terms of DFS (p = 0.08). CONCLUSION: Assessing subcellular patterns of Maspin expression in LSCC specimens could identify patients less likely to respond to PORT, who might benefit from combined chemo-radiotherapy to improve the efficacy of adjuvant protocols.

Uni- and multivariate models for investigating potential prognostic factors in idiopathic sudden sensorineural hearing loss.

With a worldwide incidence estimated at 8-15 per 100,000 population a year, idiopathic sudden sensorineural hearing loss (ISSHL) is a common clinical finding for otologists. There is a shortage of information on the clinical factors capable of predicting hearing recovery and response to therapy. The aim of the present study was to retrospectively investigate the prognostic value of clinical variables in relation to hearing recovery, in a cohort of 117 consecutive patients with ISSHL. Clinical parameters (signs, symptoms, comorbidities and treatments) and audiometric data were analyzed with univariate and multivariate statistical approaches for prognostic purposes to identify any correlation with hearing recovery, also expressed according to the Wilson criteria. Univariate analysis showed that age and hypertension were significantly related to hearing outcome (p = 0.004 and p = 0.015, respectively). Elderly patients and those with hypertension were at higher risk of experiencing no hearing recovery (OR = 3.25 and OR = 2.89, respectively). Age was an independent prognostic factor on multivariate analysis (p = 0.007). Tinnitus as a presenting symptom showed a trend towards an association with hearing recovery (p = 0.07). The treatment regimen, the time elapsing between the onset of symptoms and the start of therapy (p = 0.34), and the duration of the treatment (p = 0.83) were unrelated to recovery on univariate analysis. Among the parameters considered, only age was significantly and independently related to hearing outcome. There is a need for well-designed, randomized clinical trials to enable an evidence-based protocol to be developed for the treatment of ISSHL.

Endoglin (CD105) expression in sinonasal polyposis.

Despite appropriate surgical therapy, 5-10 % of patients with chronic rhinosinusitis (CRS) and nasal polyps (NP) experience disease recurrences. It has been suggested that angiogenesis may relate to the pathogenesis and prognosis of CRS with NP. Endoglin (CD105) is a component of the receptor complex of transforming growth factor-beta, a pleiotropic cytokine that modulates angiogenesis. A series of patients treated surgically for CRS with NP was analyzed to assess the relationship between CD105 expression, main clinicopathological features, and recurrence rate. The immunohistochemical expression of CD105 was assessed in 70 patients consecutively operated for CRS with NP. In the univariate setting, the presence of CD105 (1/0) showed a trend towards a significant association with increasing NP dimensions (p = 0.054). Intensity of CD105 reaction was also significantly associated with NP size (0.04) and with an eosinophilic histology (p = 0.048). In our multivariate setting, only asthma (p = 0.016), hypereosinophilia (p = 0.022), and preoperative polyposis score (p = 0.046) retained their independent prognostic significance in relation to NP recurrence. Further efforts are needed to elucidate the biological, angiogenic and proliferative mechanisms behind recurrent NP. Our preliminary results support the clinical utility of extra postoperative care, in terms of closer follow-ups and medication with oral anti-histamines, topical and/or oral steroids, and antileukotrienes in patients with asthma, advanced nasal polyposis at presentation, and serum hypereosinophilia.

A panel of biomarkers for predicting response to postoperative RT for laryngeal cancer?

OBJECTIVES: Postoperative radiotherapy (PORT) improves locoregional control and survival rates for patients with advanced laryngeal carcinoma (LSCC), but reported outcomes after PORT for LSCC vary considerably. Predictive markers (including biomarkers) are needed for LSCC to orient the choice of the most appropriate adjuvant therapy for individual patients. The aim of this study was to identify a panel of LSCC tissue markers (considering EGFR, mTOR, survivin, Bcl-2, angiogenin, endoglin [CD105], nm23-H1) capable of pinpointing patients at higher risk of recurrence among 33 LSCC cases treated with PORT. METHODS/RESULTS: Univariate analysis found 4 biomarkers (mTOR, nuclear survivin, CD105, non-nuclear nm23-H1) significantly associated with LSCC recurrence. A collinearity emerged between mTOR and CD105 expressions. The predictive role of two different panels (panel 1: mTOR, nuclear survivin, non-nuclear nm23-H1; panel 2: CD105, nuclear survivin, non-nuclear nm23-H1) was considered. According to the Hosmer and Lemeshow scale, panel 1 demonstrated an outstanding discriminatory power (AUC 0.903) in predicting LSCC recurrence after PORT. Panel 2 had an excellent discriminatory power too (AUC 0.899). CONCLUSIONS: Both panels of biomarkers showed an important discriminatory power in pinpointing patients at higher risk of recurrence after PORT for LSCC who could reasonably benefit from adjuvant postoperative chemo-RT.

The EGFR-mTOR pathway and laryngeal cancer angiogenesis.

Epidermal growth factor receptor (EGFR) is a trans-membrane tyrosine kinase taking part in cell transformation and tumor progression. One of the downstream pathways controlled by EGFR involves the mammalian target of rapamycin (mTOR), a proto-oncogene activated in several cell functions. Recent evidence seems to confirm that both EGFR and mTOR regulate angiogenesis. The aim of this study was to investigate the expression of EGFR and mTOR in laryngeal squamous cell carcinoma (LSCC) cells in a retrospective clinical setting and their correlation with tumor neo-angiogenesis, judged on the grounds of CD105-assessed microvascular density (MVD), and prognosis. We considered 76 consecutive patients with LSCC treated with surgery alone. Immunohistochemical expressions of EGFR, mTOR, and CD105 were measured using image analysis and findings underwent statistical analysis using univariate and multivariate models. We found that nodal status correlated significantly with patient prognosis in terms of disease-free survival (DFS) (p = 0.01). There was a strong direct correlation between mTOR and EGFR expression (p = 0.0003), and between mTOR and CD105-assessed MVD (p = 0.0025). Patients with a CD105-assessed MVD >5.28 % had a significantly higher recurrence rate (RR) (p = 0.026), and a significantly shorter DFS (p = 0.025). On multivariate analysis, only N stage [hazard ratio (HR) 3.54, p = 0.009] and CD105-assessed MVD (HR 2.87, p = 0.027) maintained their independent prognostic significance in terms of DFS. Judging from our promising findings, the EGFR-mTOR pathway should be investigated further to understand its role in LSCC neo-angiogenesis.

Personalized Treatment Strategies via Integration of Gene Expression Biomarkers in Molecular Profiling of Laryngeal Cancer.

Laryngeal cancer poses a substantial challenge in head and neck oncology, and there is a growing focus on customized medicine techniques. The present state of gene expression indicators in laryngeal cancer and their potential to inform tailored therapy choices are thoroughly examined in this review. We examine significant molecular changes, such as TP53, CDKN2A, PIK3CA, and NOTCH1 mutations, which have been identified as important participants in the development of laryngeal cancer. The study investigates the predictive and prognostic significance of these genetic markers in addition to the function of epigenetic changes such as the methylation of the MGMT promoter. We also go over the importance of cancer stem cell-related gene expression patterns, specifically CD44 and ALDH1A1 expression, in therapy resistance and disease progression. The review focuses on indicators, including PD-L1, CTLA-4, and tumor mutational burden (TMB) in predicting immunotherapy responses, highlighting recent developments in our understanding of the intricate interactions between tumor genetics and the immune milieu. We also investigate the potential for improving prognosis accuracy and treatment selection by the integration of multi-gene expression panels with clinicopathological variables. The necessity for uniform testing and interpretation techniques is one of the difficulties, in implementing these molecular insights into clinical practice, that are discussed. This review seeks to provide a comprehensive framework for promoting personalized cancer therapy by combining the most recent data on gene expression profiling in laryngeal cancer. Molecularly guided treatment options may enhance patient outcomes.

Expression of the tumour-suppressor maspin in temporal bone carcinoma.

AIMS: Although it accounts for fewer than 0.2% of all head and neck tumours, temporal bone squamous cell carcinoma (SCC) is an aggressive malignancy with a poor prognosis in advanced cases. Novel therapeutic strategies should be developed focusing on specific targeted therapies. Maspin is a serpin showing tumour-suppressing activity which has therapeutic potential. The present study is the first to investigate maspin expression in temporal bone SCCs, using a series of 29 cases. METHODS AND RESULTS: Cytoplasmic maspin expression was significantly higher in the group of patients whose SCC did not recur than in the group experiencing recurrences (P = 0.029), and in G1-G2 SCCs than in G3 cases (P = 0.001). cT correlated with recurrence rate (P = 0.05), disease-free survival (DFS) (P = 0.008) and disease-specific survival (DSS) (P = 0.0043), and pT and pathological regional lymph node status correlated with recurrence rate (P = 0.008 and P = 0.03, respectively), DFS (P = 0.017 and P = 0.0049, respectively) and DSS (P = 0.008 and P = 0.0009, respectively). CONCLUSIONS: Although further studies using larger series are required, our preliminary findings suggest that cytoplasmic maspin expression has promise as a prognostic indicator of disease recurrence in temporal bone SCC, and that reactivating maspin functions in association with apoptosis-inducing or anti-angiogenic chemotherapeutic agents might be an important goal in the treatment of temporal bone SCC.

Relationship between anti-apoptotic proteins survivin and Bcl-2, and response to treatment in patients undergoing post-operative RT for laryngeal cancer: a pilot study.

BACKGROUND: Clinicopathological research has focused on identifying molecular and biological prognostic factors for laryngeal carcinoma (LSCC) treated with post-operative radiotherapy (RT). The aim of this study was to assess the prognostic importance of anti-apoptotic proteins survivin and B-cell lymphoma-2 (Bcl-2) in a series of patients with LSCC who had primary surgery followed by RT. METHODS: Thirty-three consecutive patients who underwent primary surgery followed by RT were considered. Survivin nuclear and cytoplasmic expressions and Bcl-2 expression were determined immunohistochemically. RESULTS: The loco-regional recurrence rate was significantly higher among LSCC patients with a nuclear survivin expression >10.0% (P = 0.029), and their disease-free survival (DFS) was shorter than in cases whose nuclear survivin expression was ≤10.0% (P = 0.002). DFS was significantly shorter in cases with a Bcl-2 expression >2.0% than in those whose Bcl-2 expression was ≤2.0% (P = 0.035). CONCLUSIONS: Nuclear survivin expression and Bcl-2 expression warrant further investigation as potential predictive biomarkers to enable individualized treatments (e.g. post-operative chemo-radiotherapy instead of RT alone for patients whose LSCCs strongly express nuclear survivin or/and Bcl-2). This preliminary evidence justifies the design of new studies on the association of agents targeting survivin and Bcl-2 with conventional chemotherapeutic agents and RT for advanced LSCC.

Prognostic value of hypoxia-inducible factors (angiogenin and endoglin) in open partial laryngectomies: uni- and multivariate analyses.

PURPOSE: Advances in transoral laser microsurgery, radiotherapy, and chemotherapy (and their combinations) have reduced the indications for open partial laryngectomies, although they have replaced total laryngectomies in selected advanced or recurrent laryngeal squamous cell carcinomas (LSCCs). Tissue hypoxia in malignancies appears to be strongly associated with tumor cell invasiveness and metastases. Whether hypoxia-inducible factors can contribute to a rational recommendation of open partial laryngectomy should be investigated. MATERIALS AND METHODS: Fifty consecutive patients who had undergone primary open partial laryngectomy (supraglottic and supracricoid laryngectomies) were investigated, measuring the immunohistochemical expression of the hypoxia-inducible proteins angiogenin and endoglin in their primary LSCCs also with image analysis. RESULTS: Univariate analysis showed a significantly higher recurrence rate (P = .007) and shorter disease-free survival (P = .0047) in patients with LSCC with endoglin expression more than 9.0%. Multivariate analysis found endoglin expression independently prognostic in terms of disease-free survival (P = .012). Angiogenin expression (in carcinoma or endothelial cells) was not associated with prognosis. CONCLUSIONS: Endoglin should be further studied as a biomarker of patients with LSCC at higher risk for recurrence after open partial laryngectomy who may benefit from more aggressive treatments. Endoglin expression in positive laryngeal biopsies may prove useful as a parameter for choosing between different surgical and multimodality approaches to controversial LSCC cases.

A prognostic role for Nm23-H1 in laryngeal carcinoma treated with postoperative radiotherapy: an introductory investigation.

Postoperative RT is generally recommended for laryngeal carcinomas (LSCCs) at high risk of recurrence after surgery. There are currently no clinicopathological parameters available to predict response to such adjuvant RT in LSCC, and only a few potentially predictive biomarkers have been investigated. Nm23-H1 protein is reportedly related to the tumor cells' metastatic potential, and low Nm23-H1 expression levels in human carcinomas often correlate with a poor prognosis. The novel aim of the present preliminary study was to investigate the prognostic value of Nm23-H1 expression and subcellular localization in a series of patients given postoperative RT for LSCC. A retrospective clinicopathological investigation was conducted at an academic tertiary referral center of 28 consecutive patients given postoperative RT for LSCC. Image analysis of immunohistochemical reactions was performed to measure Nm23-H1 total and nuclear expression levels. Disease-free survival (DFS) was significantly shorter among LSCC patients with total Nm23-H1 levels <50.0 % (p = 0.03); the mean total Nm23-H1 expression was lower in patients with recurrent disease than in patients without it (statistical trend, p = 0.07). The disease recurrence rate was significantly higher (p = 0.021) and the DFS shorter (statistical trend, p = 0.052) among LSCC patients with nuclear Nm23-H1 levels <5.0 %. The locoregional recurrence-risk ratio in LSCC patients with nuclear Nm23-H1 levels <5.0 % was 9.16. Nm23-H1 warrants further investigation of its potential role as a predictive biomarker with a view to providing tailored treatments after surgery, such as combinations of chemotherapy and RT instead of RT alone, in patients whose LSCCs have low or no Nm23-H1 expression.