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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., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

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., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objectives: To identify pre-operative radiological parameters that are able to predict the functional outcomes of open partial horizontal laryngectomy (OPHL)., Methods: The present retrospective study concerned a cohort of 96 patients with laryngeal squamous cell carcinoma who underwent pre-operative radiological staging with contrast-enhanced computerised tomography of the neck, and subsequent supracricoid or supratracheal laryngectomy. Univariate and multivariate analyses were run to assess the prognostic value of the main demographic and surgical variables, and the pre-operative cephalometric values, respectively, in terms of predicting patients' functional outcomes., Results: Multivariate analysis showed that a larger anteroposterior cross-sectional dimension of the aero-digestive tract in the mid-retroglossal area, and a greater distance between the genial tubercle and the hyoid bone in the mid-sagittal plane correlated significantly with better functional outcomes in terms of decannulation rate at discharge., Conclusions: Our findings show that larger pre-operative upper aero-digestive tract diameters and volumes coincide with better post-operative functional outcomes after OPHL., (Copyright © 2023 Società Italiana di Otorinolaringoiatria e Chirurgia Cervico-Facciale, Rome, Italy.)

Background: To retrospectively evaluate oncological outcomes in two groups of patients with pT4aN0 glottic SCC treated with total laryngectomy (TL) and neck dissection (ND) who underwent postoperative radiotherapy or exclusive clinical and radiological follow-up., Methods: It includes patients with pT4N0 glottic SCC who underwent TL and unilateral or bilateral ND with or without PORT. Divided in two comparison groups: the first group underwent adjuvant RT (TL-PORT); the second group referred to clinical and radiological follow-up (TL)., Results: PORT was associated with a better OS while no differences were found in terms of DSS. A better local control is achieved when PORT is administered while no differences in terms of regional and distant control rates were found. Bilateral ND positively impacts on the regional control while the PNI negatively impact the regional control., Conclusions: A tailored PORT protocol might be considered for pT4N0 glottic SCC treated with TL and ND, both considering the ND's extent and presence of PNI., (© 2022 The Authors. Head & Neck published by Wiley Periodicals LLC.)

Purpose: To evaluate the functional and oncologic outcomes of adjuvant (chemo)radiation [(C)RT] after open partial horizontal laryngectomies (OPHLs)., Methods: Multicenter retrospective evaluation of 130 patients (116 males, 14 females) submitted between 1995 and 2017 to OPHL Types II and III for laryngeal cancer and receiving adjuvant (C)RT for one or more of the following risk factors at histopathologic examination of the surgical specimen: pT4a and/or > pN2a categories, close/positive resection margins, or presence of both perineural (PNI) and lympho-vascular invasion (LVI). The primary study endpoints were evaluation of the presence of tracheostomy and/or gastrostomy at last follow-up, and calculation of laryngo-esophageal dysfunction-free survival (LEDFS)., Results: Mean age of the study cohort was 60.8 ± 8.9 years (median, 62; interquartile range [IQR], 13). Mean follow-up was 50.7 ± 39.4 months (range 24-188; median, 38; IQR, 51). Adjuvant therapy consisted of CRT in 53 (41%) patients, and RT alone in 77 (59%). Five-year LEDFS was 85%. Overall survival was 71.5%, while 13% of patients remained tracheostomy- and 3% gastrostomy-dependent at the last follow-up. The only significant variable in predicting survival (p = 0.020) was tracheostomy dependence: it was maintained in 7.5% of subjects after OPHL Type II and in 34% of those submitted to OHPL Type III (p < 0.001)., Conclusions: In selected patients affected by advanced laryngeal cancer, OPHLs Type II and III have a relatively good laryngeal safety profile and provide favorable oncologic outcomes even in case of need for adjuvant (C)RT., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature.)

Objectives: The primary aim of the present study was to report our multi-institutional experience in surgical salvage with open partial horizontal laryngectomies (OPHL) after failed radiotherapy (RT) for laryngeal squamous cell carcinoma (LSCC). Secondary aims were to analyze the prognostic meaning of the main clinical and pathological parameters in relation to the oncologic outcome and to compare our results with the available literature., Study Design: A retrospective multicenter analysis of surgical oncological outcomes., Methods: We retrospectively review the clinical charts of 70 recurrent LSCC patients after primary RT failure undergone salvage OPHL., Results: At last follow-up, 46 patients (65%) were disease-free; six (9%) were alive with disease; nine (12%) died because of the disease; and nine (12%) died without evidence of disease. The final local control, overall survival, disease-specific survival, and laryngectomy-free survival were 87%, 75%, 87%, and 91%, respectively. Twelve patients (17%) experienced postoperative complications, whereas 18 patients (25%) experienced late sequelae. In five patients (7%), decannulation was not possible because of postoperative laryngeal stenosis., Conclusion: In selected patients, when proper selection criteria for conservation laryngeal surgery are adopted, OPHL can be considered for salvage after RT failure., Level of Evidence: 4 Laryngoscope, 130:431-436, 2020., (© 2019 The American Laryngological, Rhinological and Otological Society, Inc.)

Background: The involvement of the thyroarytenoid (TA) muscle by glottic cancer may be related to an impaired vocal cord mobility, which is classified as cT2 disease. The primary endpoint was to evaluate the prognostic significance of TA muscle involvement in early glottic cancer treated with transoral laser microsurgery (TLM)., Methods: A review was conducted on a cohort of 209 patients consecutively treated with TLM for early glottic carcinoma. Univariate analysis was used to examine the prognostic meaning of clinical and pathological parameters., Results: The statistical analysis showed that TA muscle infiltration correlated significantly with a worse prognosis in terms of recurrence rate and disease-free survival, and this was confirmed even in the subcohort with pT1a glottic cancer., Conclusions: Our preliminary findings suggest that it could be considered as a criterion for upstaging a glottic cancer from pT1 to pT2., (© 2019 Wiley Periodicals, Inc.)

Background: Given the relevance of any tumor invasion of the arytenoid cartilage or crico-arytenoid unit to the planning open partial horizontal laryngectomy (OPHL) for laryngeal squamous cell carcinoma (LSCC), it is important to have a reliable radiological test to assess impairments of these structures., Methods: We retrospectively compared the endoscopic, radiological, and pathological findings in patients with glottic LSCC who underwent OPHL., Results: The endoscopic finding of a reduced (impaired or absent) vocal cord motility proved more sensitive, with better positive and negative predictive values, but less specific than the radiological finding of complete arytenoid sclerosis in detecting histologically assessable infiltration of the arytenoid cartilage., Conclusions: Endoscopy retains a key role in the preoperative workup for glottic LSCC. CT evidence of complete sclerosis of the arytenoid cartilage is related to a dangerous contiguity of the tumor to the cartilage., (© 2018 Wiley Periodicals, Inc.)

Background: The purpose of this retrospective study was to identify subcategories in cT3 to cT4a supraglottic/glottic cancers, describing their different spreading patterns, and local and locoregional recurrence modes., Methods: Four hundred eighty-nine patients who underwent open partial horizontal laryngectomies (OPHLs) were retrospectively classified as: subcategory I (anterior pT3 with normal arytenoid mobility); subcategory II (posterior pT3 with impaired/absent mobility); subcategory III (anterior pT4 with normal mobility); and subcategory IV (posterior pT4 with impaired/absent mobility)., Results: Five-year overall survival (OS), disease-specific survival (DSS), disease-free survival (DFS), locoregional, local control, freedom from laryngectomy, and laryngectomy-free survival were significantly better in anterior tumors (subcategories I and III) when compared with the corresponding posterior ones (subcategories II and IV)., Conclusion: Anterior cT3 tumors are manageable by OPHL, and this approach could also be proposed in the treatment of early anterior cT4aN0. Despite promising results, OPHLs should be considered under investigation in posterior cT3 tumors due to clinical and biological behavior similar to cT4a tumors., (© 2018 Wiley Periodicals, Inc.)

Background: Major pharyngeal defects after total pharyngolaryngectomy for hypopharyngeal squamous cell carcinoma (SCC) frequently demand reconstruction strategies that include myocutaneous pedicled flaps, such as the pectoralis major flap., Methods: We retrospectively reviewed the clinical charts of 24 patients with hypopharyngeal SCC treated with Bocca's hemipharyngo-total laryngectomy (HPTL) at our Institution., Results: Eighteen patients (80%) experienced no disease recurrence after primary surgery and were alive with no evidence of disease after a mean follow-up of 43 months. The 2-year overall survival (OS) and disease-specific survival (DSS) rates in our sample were 69% and 82%, respectively., Conclusion: Bocca's HPTL enables an immediate neopharyngeal reconstruction, and is indicated in selected patients with intermediate to advanced hypopharyngeal tumors., (© 2018 Wiley Periodicals, Inc.)

Objectives: To evaluate the effect of preepiglottic space (PES) dissection in the endoscopic supraglottic laryngectomy (ESL)., Study Design: A retrospective cohort study., Methods: We retrospectively compared 15 patients who underwent ESL with 15 patients matched for clinical stage who underwent open partial horizontal laryngectomy (OPHL). The functional outcomes were assessed in terms of hospital stay; need for nasal feeding tube (NFT) and tracheostomy, as well as duration of their use; postoperative complications; aspiration pneumonia rates; voice quality; and dysphagia., Results: Among the ESL cases, combined dissection of the epiglottis and PES (type III) had a negative impact on functional outcomes. ESL patients experienced shorter hospital stays, as well as shorter use of NFT and tracheostomy, than patients who had OPHL., Conclusion: Combined dissection of the epiglottis and PES (ESL type III) negatively affected functional outcome in patients undergoing ESL, a procedure generally related to significantly better functional outcomes than OPHL type I., Level of Evidence: 4. Laryngoscope, 128:1371-1378, 2018., (© 2017 The American Laryngological, Rhinological and Otological Society, Inc.)

Background: The purpose of this study was to present our findings on the involvement of paratracheal lymph nodes in laryngeal squamous cell carcinoma (SCC) with subglottis extension, which is controversial., Methods: We assessed 196 patients with laryngeal SCC involving the subglottis, treated with open laryngeal surgery with or without paratracheal neck dissection (PTND). The relationship of the paratracheal lymph node metastatic pattern with laterocervical nodal status and tumor location within different subglottic subsites was analyzed. The influence of PTND on regional disease control was assessed., Results: Paratracheal lymph nodes were affected in 12.2% of cases. An increased frequency (P = .064) of paratracheal metastasis was noticed in case of anterior subglottis extension with respect to other subsites. A correlation (P < .001) between paratracheal lymph node and laterocervical node involvement was found among subjects with posterior subglottic extension., Conclusions: Prophylactic PTND is indicated in laryngeal SCC with anterior subglottic extension and/or posterior subglottis involvement with clinically apparent laterocervical node metastases., (© 2017 Wiley Periodicals, Inc.)

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, ((c) patients unfit for or refusing chemoradiotherapy.)

Background: Treatment for local glottic cancer recurrences after primary transoral laser microsurgery (TLM) has not been standardized., Methods: In 33 consecutive cases of salvage TLM after laser surgery for early glottic carcinoma failed, we retrospectively considered the potential clinicopathological prognostic factors in univariate statistical setting., Results: Patient age <65 years and pathological involvement of the deep margins were associated with a higher second recurrence rate and shorter disease-free survival., Conclusion: The age of the patient and the pathological status of surgical margins after salvage TLM could be useful for planning a closer endoscopic/radiological follow-up in selected patients at high risk of recurrence. Other appropriately designed studies are needed to see if an open surgical approach should be considered for younger patients (<65 years old) with recurrent glottic carcinoma after primary TLM. © 2016 Wiley Periodicals, Inc. Head Neck 38: 1043-1049, 2016., (© 2016 Wiley Periodicals, Inc.)

Background: Laryngeal squamous cell carcinoma (SCC) accounts for 1.9% of cancers worldwide. Most of these are diagnosed in the early stages (T1-T2, and N0). For these, a larynx preserving/conserving option is preferable. Beyond transoral laser microsurgery (TLM), open partial horizontal laryngectomy is a function-sparing surgical technique used to treat laryngeal SCC., Methods: We retrospectively analyzed the clinical outcomes of 216 patients who underwent open partial horizontal laryngectomy for glottic cT2 laryngeal cancer., Results: Five-year overall survival (OS), disease-specific survival (DFS), locoregional control, local control, laryngeal function preservation, and laryngectomy-free survival rates were 93.1%, 98.0%, 97.1%, 97.5%, 97.8%, and 98.5%, respectively. Disease controls were significantly affected by previous treatment and type of surgery used., Conclusion: Although TLM for cT2 laryngeal cancer with unimpaired vocal cord mobility still represents a sound option, open partial horizontal laryngectomy offers higher local control and laryngeal preservation rates for selected patients with impaired mobility of vocal cords combined with involvement of the paraglottic space. © 2015 Wiley Periodicals, Inc. Head Neck 38: E333-E340, 2016., (© 2015 Wiley Periodicals, Inc.)

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.

Background: There are limited data on the role of laser-assisted surgery for early glottic cancer in elderly patients., Methods: This retrospective study was conducted on a series of 130 consecutive cases of early glottic carcinoma occurring in elderly patients (>65 years old) treated with CO(2) laser surgery., Results: The overall and disease-specific survival rates were 87.7% and 99.2%, respectively. The rates of local disease control after primary laser surgery, ultimate local control with laser alone, and laryngeal preservation were 84.6%, 93.8%, and 96.9%, respectively. A shorter disease-free survival (DFS) was associated with the involvement of 1 or more specific laryngeal regions (arytenoids, ventricle, anterior commissure, vocal muscle, subglottis) (p = .01) and the status of the surgical margins (p = .002); on multivariate analysis, only the latter remained prognostically significant vis-à-vis the DFS (p = .002)., Conclusions: Even in elderly patients with early glottic carcinoma, endoscopic laser surgery is an effective treatment., (Copyright © 2012 Wiley Periodicals, Inc.)

Objective: Assess the impact of surgical margin CO2 laser photocoagulation (LPC) on disease local control in patients submitted to endoscopic surgery for early glottic cancer in comparison with subjects treated with laser cordectomy without borders LPC., Study Design: Historical cohort study., Setting: Regional referral cancer center., Subjects and Methods: A total 281 patients with early glottic cancer (T1a, T1b, T2) were treated with endoscopic laser cordectomy according to the European Laryngological Society Classification between 1999 and 2006. Among the patients, 123 (treated between 2003 and 2006) were submitted to postresection LPC of surgical margins (group 1), whereas 158 (operated between 1999 and 2002) underwent laser cordectomy without margin LPC (group 2). Median follow-up was 51 months (range, 36-101 months)., Results: Local recurrence was found in 43 of 281 (15.30%) subjects (18 with T1a, 13 with T1b, 12 with T2). A significant difference in recurrence rate was found among patients treated with margin LPC in comparison with group 2 (P = .022). In particular, a lower recurrence rate in LPC patients was noticed in case of close (≤ 1 mm), nondefinable, and positive margins with infiltration of the superficial border. No significant difference was noticed in the case of negative edges (>1 mm) or involvement of either deep margin or both superficial and deep edges., Conclusions: Surgical margin LPC increases disease local control in the case of close and superficial margin positivity. In such cases, no further treatment (surgical revision or radiotherapy) seems to be required in LPC patients. In case of deep border involvement, surgical revision or radiotherapy should be performed.

The aim of the present investigation was to analyze the oncological results of a series of early stage glottic carcinomas treated with CO(2) laser-assisted endoscopic surgery. We focused on prognosis factors with significant impact on local control and disease-free survival (DFS). This retrospective study was conducted on a series of 177 consecutive patients with pT1-T2 glottic carcinomas treated with CO(2) laser-assisted endoscopic surgery in the period 2000-2007. All considered patients had at least a 24-month follow-up period (mean follow-up 49.1 ± 23.0 months). The overall survival and the disease-specific survival rates were respectively 90.8 and 98.8%. The rates of local control with primary laser surgery, ultimate local control with laser alone, and laryngeal preservation were 86.3, 94.3, and 97.7%, respectively. Arytenoids (p = 0.006) and limited subglottic involvements (p = 0.0002) have a significant impact on DFS. Endoscopic laser surgery is the gold standard in the treatment of early glottic carcinoma because of high local control rates with laser alone, day surgery modality, very low morbility, good post-operative voice quality in most of the cases, and low costs.

Despite advances in laryngeal squamous cell carcinoma (LSCC) treatment, patient survival has not improved in the last two decades. Novel, more effective strategies should be based on receptor-mediated LSCC-targeted therapy. The epidermal growth factor receptor (EGFR) is the most widely studied molecular target. MASPIN multifaceted anti-tumor effects have been rarely evaluated in LSCC. The aims of this study were to investigate EGFR and MASPIN expression and the role of sub-cellular MASPIN localization in LSSC. MASPIN and EGFR expression and the sub-cellular localization of MASPIN were assessed using a computerized image analysis system in 108 consecutive cases of operable LSCC. The rates of occurrence of lymph node metastases and recurrent disease were lower in patients with a nuclear pattern of MASPIN expression (p = 0.004, p = 0.0028). As expected, the loco-regional recurrence rate was lower in N0 patients (p = 0.009), but the disease recurrence rate was even lower in N0 patients with a nuclear localization of MASPIN (p = 0.020). Disease-free survival was longer in cases of LSCC with a nuclear MASPIN pattern (p = 0.003). The intensity of EGFR reactivity and the EGFR area fraction were unrelated to the clinico-pathological and prognostic parameters in LSCC. A nuclear MASPIN pattern is a promising prognostic indicator in LSCC, but further evidence is needed before elective neck dissection can be considered for cN0 LSCCs with a non-nuclear MASPIN pattern. Although a better understanding of the mechanisms behind sub-cellular MASPIN localization is mandatory, re-activating nuclear MASPIN in association with specific chemotherapeutic agents may be an important goal in the treatment of LSCC.

Conclusions: Survivin expression should be studied as a potential hallmark of higher risk oral, oropharyngeal and laryngeal squamous cell carcinomas (SCCs) to develop loco-regional recurrences. These outcomes could have a significant impact on both the treatment modalities and the intensity of post-treatment follow-up. Further investigation is necessary before considering elective neck dissection in patients with laryngeal SCC with high survivin expression., Objectives: Functioning simultaneously at cell division and apoptosis inhibition, survivin, a member of the inhibitor of apoptosis proteins family, plays a pivotal role in determining cell survival. Significant over-expression of survivin has been demonstrated in most human malignancies and correlated with more aggressive forms. This review focuses on the attempts to translate survivin biologic properties toward both a diagnostic/prognostic tool and a novel therapeutic target in head and neck SCC (HNSCC)., Materials and Methods: An exhaustive review of literature was performed to investigate available evidence about survivin expression, biological role and therapeutic potential in HNSCC., Results: Multiple evidence indicates that, in HNSCC cell lines, survivin inhibition by gene therapy and by small molecule inhibitors significantly increases the anti-tumour activity of several cytotoxic and other targeted therapies.

Conclusions: Our very preliminary results support the hypothesis that MASPIN expression in primary head and neck squamous cell carcinoma (HNSCC) may be a valuable parameter for predicting patients' responses to a treatment based on carboplatin plus vinorelbine combined with radiotherapy., Objectives: The roles of induction chemotherapy and combined chemoradiotherapy in the treatment of locally advanced unresectable HNSCCs have evolved rapidly. MASPIN has a unique tumour-suppressing activity. Experimental evidence has shown that MASPIN suppresses tumour growth, angiogenesis, invasion and metastasis. We investigated the potential prognostic roles of MASPIN and p53 in a series of HNSCCs treated with carboplatin plus vinorelbine combined with radiotherapy., Patients and Methods: Nineteen consecutive stage III or IV HNSCC patients were recruited. The treatment plan consisted of the administration of carboplatin on day 1 and vinorelbine on days 1 and 8. Four weeks later, carboplatin was administered concomitantly with radiation therapy. Expression of MASPIN and p53 was determined immunohistochemically in HNSCC diagnostic biopsies., Results: A significant inverse relation was found between MASPIN expression and cN staging (p = 0.003). From a prognostic viewpoint, MASPIN expression was directly correlated with chemoradiotherapy response (p = 0.041). Moreover, the log-rank test showed a significant relationship between higher MASPIN expression and longer disease-free survival (p = 0.03), overall survival (p = 0.006) and disease-specific survival (p = 0.007).

MASPIN, a member of serpin superfamily, has multifaceted biological functions and an unique tumour suppressing activity. Experimental evidences showed that MASPIN suppresses tumour growth, angiogenesis, invasion and metastasis. Only a very limited number of studies considered MASPIN expression in the upper aero-digestive tract carcinomas. It was recently found that nuclear localization of MASPIN was significantly associated with lower recurrence rate and longer disease-free interval in laryngeal carcinoma. The present study investigated the biological and prognostic role of MASPIN in relation to its subcellular localization in oral carcinoma. Sub-cellular pattern of distribution of MASPIN, nuclear and cytoplasmic MASPIN expressions were immunohistochemically determined in 56 consecutive cases of oral carcinoma. Statistical analysis found a significant association between pN-stage and recurrence of disease (P=0.032) and a significantly longer disease-free interval in pN0 patients than in pN+ ones (P=0.038). None of the subcellular expressions of MASPIN was significantly correlated with recurrence of disease and disease-free interval in our series of oral carcinomas. Sixty-one percent of pN0 cases was strongly MASPIN-positive in the cytoplasm of primary carcinoma cells, 33% of the pN+ cases was MASPIN-positive in the cytoplasm. Statistical analysis found a significant association between MASPIN cytoplasmic expression and pN-stage (P=0.032). Negative MASPIN immunoreactivity in carcinoma cells cytoplasm may be useful to identify patients at risk of disease disseminating to neck lymph nodes. Further investigations are necessary to understand the biological role of cytoplasmic MASPIN localization in oral carcinoma.

Objective: Considerable evidence has confirmed that p27 protein plays a negative role in cell-cycle progression from the G1 to the S phase and is considered a tumour suppressor. p27 down-regulation was demonstrated in several malignancies. Only a few studies investigated p27's potential prognostic role in laryngeal squamous cell carcinoma (SCC). The aim of the present study was to determine the prognostic relevance of p27 expression in a cohort of laryngeal SCCs that were very homogeneous from a treatment viewpoint to avoid possible influences of treatment modalities on results; all patients underwent only partial laryngectomy on the primary lesion. We simultaneously investigated monoclonal antibody against a proliferating cell associated epitope MIB-1 expression., Design and Methods: Twenty-two cases of laryngeal SCC that had undergone exclusive supracricoid or supraglottic laryngectomies with or without neck dissection at the Department of Otolaryngology of Padova University were evaluated. Primary laryngeal SCC p27 reactivity and MIB-1 reactivity were immunohistochemically tested and evaluated by a workstation image analysis system., Main Outcome Measures: A lesion was considered p27 positive when more than 18.56% of the tumour cells showed diffuse strong staining. Samples with > 20.24% of stained cells were considered MIB-1 positive., Results: The mean p27 expression was 17% and 22% in patients with and without disease recurrence, respectively. Low p27 expression was statistically associated with disease recurrence (p = .045); on the other hand, high MIB-1 values were associated with SCC recurrence after treatment (p = .045)., Conclusions: The intervals of confidence analysis showed a stronger relationship of MIB-1 versus p27 in predicting disease recurrence in our cohort of patients treated only with partial laryngectomies.

Background: Survivin is the smallest mammalian member of the inhibitor of apoptosis (IAP) proteins family. The aim of the present study was to determine survivin expression in laryngeal squamous cell carcinoma (SCC) and in neck lymph node metastases. The survivin value in predicting prognosis in laryngeal SCC was also investigated., Patients and Methods: Survivin expression was investigated in 37 laryngeal SCCs and in 12 cervical lymph node metastases., Results: A nuclear reaction predominated in laryngeal SCCs. Survivin expression was significantly higher in pN+ laryngeal SCCs than in pN0 (p = 0.017). Survivin expression was higher in cervical lymph node metastases than in correspondent primary laryngeal SCCs (p = 0.002). Survivin expression in laryngeal SCCs that developed loco-regional recurrence was significantly higher than in laryngeal SCCs without recurrence of disease (p = 0.039)., Conclusion: Nuclear expression of survivin should be studied as a hallmark of higher risk laryngeal SCCs to develop loco-regional recurrences. Higher survivin expression in pN+ laryngeal SCC may suggest elective neck dissection in clinically N0 patients with high survivin expression in primary SCC. The extremely high survivin expression in lymph node metastases may support the use of survivin in the diagnosis of lymph node micro-metastases.

Conclusions: The preliminary results reported here suggest that survivin expression in primary oral and oropharyngeal squamous cell carcinomas (SCCs) may identify patients at risk of disease disseminating to neck lymph nodes. If these results are confirmed in larger series of patients it may imply that elective neck dissection should be considered in clinically N0 patients with oral and oropharyngeal SCCs who show high expression of survivin., Objective: To investigate the expression of survivin, a member of the inhibitor of apoptosis proteins family, in patients with primary oral and oropharyngeal SCCs with and without neck lymph node metastases., Material and Methods: We considered 13 consecutive cases of oral and oropharyngeal SCCs with lymph node metastases (pN + ) and 13 cases of pN0 oral and oropharyngeal SCCs. The survivin reactivity of primary SCCs and lymph node metastases was evaluated immunohistochemically. A lesion was considered positive if >9.5% of the tumour cells showed diffuse strong staining., Results: Sporadic groups of normal basal and parabasal epithelial cells showed weak survivin staining. In SCCs, a nuclear reaction predominated. Eight primary pN+ SCCs were survivin-positive (mean expression 34.7%), compared to 5 primary pN0 SCCs (mean expression 12.3%; p=0.017). Statistical analysis disclosed significantly higher survivin expression in primary oral and oropharyngeal SCCs that developed distant non-lymphatic metastases (p=0.012).