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Background: Preoperative assessment of mandibular bone invasion in squamous cell carcinoma of the oral cavity and oropharynx is crucial for optimizing bone resection. The principal aim of this study was to evaluate the diagnostic value of CT and MR imaging for the diagnosis of mandibular bone invasion compared to the histological reference. In addition, we assessed the survival impact of bone invasion., Patients and Methods: A single-center retrospective study included all consecutive patients treated by mandibular bone interruption for squamous cell carcinoma of the oral cavity and/or oropharynx., Results: Sixty-eight patients were included. Prevalence of bone invasion on histology was 43%. Sensitivity, specificity and positive and negative predictive value were respectively 70%, 71%, 66% and 76% for CT compared with histologic analysis, 83%, 50%, 59% and 78% for MRI, and 83%, 62% 62%, 83% for associated CT and MRI. The two tests showed good agreement, with kappa index 0.69 (95% CI, 0.49-0.89) (P<0.0001). There was no difference in overall survival (log-rank>0.70) between the groups with and without bone invasion., Conclusion: CT and MRI are complementary for preoperative assessment of mandibular bone invasion, be it cortical and/or medullary, and in some cases may allow mandibular bone-sparing., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

Purpose of Review: Early-stage squamous cell carcinoma of the larynx can be successfully treated with radiotherapy or surgery (transoral or open approaches). Oncologic results are comparable while functional results may be different according to the volume of resection. In some countries radiotherapy is often preferred as primary treatment. In case of recurrence, surgical salvage is the only option. Careful examination, endoscopic assessment, computed tomography or magnetic resonance imaging are necessary to assess superficial and deep extensions into the larynx, including cartilage framework and to restage the tumor., Recent Findings: The choice between endoscopic and open partial laryngectomy is based on the extension and characteristics of the tumor. Oncologic results of open approaches are encouraging as local control, survival, and laryngeal preservation rates reported in the literature are close to those obtained in nonpreviously treated patients. Functional results are not significantly worse and major complications in the previously irradiated patients undergoing open neck surgery not increased.Supracricoid partial surgery seems to be more and more performed., Summary: With regards to the results, open partial surgery, like in nonpreviously treated patients, is still indicated for the surgical treatment of postradiotherapic recurrent/persistent disease.

Background: The oncologic impact of surgical margins after transoral laser microsurgery (TLM) for T1 and T2 glottic carcinoma is controversial. The purpose of this study was to assess the prognostic value of margin status in terms of local control., Methods: Records of 266 patients treated from 1990 to 2013 were evaluated. Patients with previous cordectomy or without preoperative CT scan were excluded from the study., Results: A total 110 patients (85 T1a, 8 T1b, and 17 T2) were enrolled. A local recurrence was observed in 23 patients. Five-year disease-free survival was significantly impaired in patients with positive margins (p = .009) and in patients with deep involvement of the vocal muscle (p = .004)., Conclusion: The present study shows that invaded margin is a factor of poor local control even though laser vaporization was systematically applied after resection. In case of deep vocal fold involvement, TLM should be extended beyond the vocal muscle to improve local control. © 2016 Wiley Periodicals, Inc. Head Neck 38: 1804-1809, 2016., (© 2016 Wiley Periodicals, Inc.)

Human epidermal growth factor receptor 3 (HER3) is a member of the human epidermal growth factor receptor (HER) family. The main characteristic of HER3 is that it does not possess tyrosine kinase activity, unlike other HERs. The role of HER3 in tumorigenesis has now been recognized, particularly in head and neck squamous cell carcinomas (HNSCCs). Despite conflicting studies, HER3 was found to be overexpressed in HNSCC samples, and correlates with disease progression and poor survival, especially when it is coexpressed with other HERs. HER3 is a significant factor in HNSCC treatment resistance. Indeed, HER3 is a major mechanism described for cetuximab resistance because of modification of epidermal growth factor receptor (EGFR) internalization and by phosphotidylinositol-3-kinase (PI3K)/AKT signaling pathway activation. HER3 also affects resistance to tyrosine kinase inhibitors (TKIs) and thereby promotes treatment escape and radiotherapy resistance by activation of the survival signaling pathway. To counteract this, pharmacologic inhibitors of HER3 are currently in development and could significantly improve HNSCC treatment. © 2016 Wiley Periodicals, Inc. Head Neck 38: E2412-E2418, 2016., (© 2016 Wiley Periodicals, Inc.)

Objective: The study was designed to assess the prevalence, management and survival of patients with simultaneous squamous cell carcinomas of the oral cavity and hypopharynx (OC/HP)., Material and Methods: A multicenter, retrospective study (2 university hospitals) was conducted between 2003 and 2007 on a series of 96 patients with simultaneous squamous cell cancers of the OC/HP., Results: A total of 88 men and 8 women were included in the study: 81 patients presented double sites, 14 presented triple sites and one presented quadruple sites. The tumour sites most frequently observed were: hypopharynx in 61% of cases (involving the pyriform sinus in 42% of cases) and the oropharynx in 59% of cases (involving the palatine tonsil in 30% of cases). Upper aerodigestive tract endoscopy under general anaesthesia revealed a simultaneous lesion not suspected on clinical examination in 45% of patients: the site discovered on endoscopy was hypopharyngeal in 2 out of 3 cases; the tumour was classified T1 or T2 in 95.5% of cases. Patients treated simultaneously for all sites had a better prognosis than patients in whom each tumour was treated separately. The 5-year specific survival was 34% and the 5-year overall survival was 28%., Conclusion: The prevalence of simultaneous squamous cell carcinomas of the oral cavity and hypopharynx ranges between 1 to 7.4% in the literature and was 4.6% in the present series. A common treatment strategy for each of the patient's tumours appears to be superior to the current theoretical approach that consists of considering each tumour separately., (Copyright © 2014 Elsevier Masson SAS. All rights reserved.)

Background: Head and Neck Squamous Cell Carcinoma (HNSCC) is the sixth most common cancer worldwide. The treatment of advanced stages HNSCC is based on surgical treatment combined with radiotherapy and chemotherapy or concomitant chemo-radiotherapy. However, the 5-year survival remains poor for advanced stages HNSCC and the development of new targeted therapies is eagerly awaited. F14512 combines an epipodophyllotoxin core-targeting topoisomerase II with a spermine moiety introduced as a cell delivery vector. This spermine moiety facilitates selective uptake by tumor cells via the Polyamine Transport System (PTS) and reinforces topoisomerase II poisoning. Here we report the evaluation of F14512 toward HNSCC., Materials and Methods: Four cell lines representative of head and neck cancer localizations were used: Fadu (pharynx), SQ20B (larynx), CAL33 and CAL27 (base of the tongue). PTS activity and specificity were evaluated by confocal microscopy and flow cytometry using the fluorescent probe F17073 which contains the same spermine moiety as F14512. Cytotoxicity, alone or in association with standard chemotherapeutic agents (cisplatin, 5FU), and radio-sensitizing effects were investigated using MTS and clonogenic assays, respectively. F14512 efficiency and PTS activity were also measured under hypoxic conditions (1% O2)., Results: In all 4 tested HNSCC lines, an active PTS was evidenced providing a specific and rapid transfer of spermine-coupled compounds into cell nuclei. Interestingly, F14512 presents a 1.6-11-fold higher cytotoxic effect than the reference compound etoposide (lacking the spermine chain). It appears also more cytotoxic than 5FU and cisplatin in all cell lines. Competition experiments with spermine confirmed the essential role of the PTS in the cell uptake and cytotoxicity of F14512. Hypoxia had almost no impact on the drug cytotoxicity. The combination of F14512 with cisplatin, but not 5FU, was found to be synergistic and, for the first time, we demonstrated the significant radio-sensitizing potential of F14512., Conclusion: The spermine moiety of F14512 confers a targeted effect and a much better efficacy than etoposide in HNSCC lines. The synergistic effect observed in association with cisplatin and radiotherapy augurs well for the potential development of F14512 in HNSCC., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Purpose: The present in vivo/in vitro study was undertaken in order to evaluate the importance of macrophage migration inhibitory factor (MIF) in the progression of head and neck squamous cell carcinoma (HNSCC)., Methods: Tumor tissue expression (MIF immunostaining) and plasma levels (ELISA) of MIF were determined in HNSCC patients and correlated with tumor recurrence and metastasis, and overall survival. Furthermore, the impact of MIF expression on cell proliferation and anticancer drug sensitivity was examined in murine squamous carcinoma cell line SCCVII after MIF knockdown (MIF-KD)., Results: As revealed by quantitative analysis of MIF immunostaining, tumor progression was accompanied by an increase in mean optical density (MOD) and labeling index (LI). Likewise, an elevation of MIF serum levels was noted in HNSCC patients (n = 66) versus healthy individuals (n = 16). Interestingly, comparison of laryngeal carcinoma patients on the basis of MIF tissue expression (high expression, LI ≥ 47, versus low expression, LI < 47) disclosed a significant difference between disease-free survival curves for local and nodal recurrence, and overall survival curve. In vitro, MIF knockdown in murine SCCVII cells resulted in reduced cell proliferation and a decrease in cell motility. In mice inoculated with SCCVII cells, MIF-KD tumors grew more slowly and also appeared more sensitive to chemotherapy., Conclusions: Both clinical observations and experimental data suggest that MIF plays a pivotal role in the progression of HNSCC.

Objectives: This report presents the French Society of ORL (SFORL) guidelines for exploration for remote metastasis and synchronous second cancer in initial staging of head and neck squamous cell carcinoma., Materials and Methods: An exhaustive literature review was analyzed by a multidisciplinary work-group., Results: The thorax is the most frequent location of remote metastases and synchronous second cancer outside of the upper aerodigestive tract. Thoracic CT is recommended as first-line examination in all cases (grade B). 18-FDG PET/CT is recommended when the thoracic CT image is doubtful or in case of high metastatic risk (grade B), for the detection of non-pulmonary remote metastasis. Esophageal exploration is recommended in case of significant risk of synchronous esophageal cancer (hypopharyngeal or oropharyngeal tumor, chronic alcohol intoxication) (grade B). The reference examination is flexible endoscopy of the upper digestive tract (grade B)., Conclusion: The present grade B recommendations rationalize the roles of the various first-line radiological and endoscopic examinations for remote metastasis and synchronous second cancer, so as to limit the number of examinations performed, thereby reducing the time needed for initial staging., (Copyright © 2012 Elsevier Masson SAS. All rights reserved.)

Purpose: To compare the efficacy and safety of induction chemotherapy (ICT) followed by chemoradiotherapy (CRT) or bioradiotherapy (BRT) for larynx preservation (LP)., Patients and Methods: Previously untreated patients with stage III to IV larynx/hypopharynx squamous cell carcinoma received three cycles of ICT-docetaxel and cisplatin 75 mg/m(2) each on day 1 and fluorouracil 750 mg/m(2) per day on days 1 through 5. Poor responders (< 50% response) underwent salvage surgery. Responders (≥ 50% response) were randomly assigned to conventional radiotherapy (RT; 70 Gy) with concurrent cisplatin 100 mg/m(2) per day on days 1, 22, and 43 of RT (arm A) or concurrent cetuximab 400 mg/m(2) loading dose and 250 mg/m(2) per week during RT (arm B). Primary end point was LP at 3 months. Secondary end points were larynx function preservation (LFP) and overall survival (OS) at 18 months., Results: Of the 153 enrolled patients, 116 were randomly assigned after ICT (60, arm A; 56, arm B). Overall toxicity of both CRT and BRT was substantial following ICT. However, treatment compliance was higher in the BRT arm. In an intent-to-treat analysis, there was no significant difference in LP at 3 months between arms A and B (95% and 93%, respectively), LFP (87% and 82%, respectively), and OS at 18 months (92% and 89%, respectively). There were fewer local treatment failures in arm A than in arm B; salvage surgery was feasible in arm B only., Conclusion: There is no evidence that one treatment was superior to the other or could improve the outcome reported with ICT followed by RT alone (French Groupe Oncologie Radiothérapie Tête et Cou [GORTEC] 2000-01 trial [Induction CT by Cisplatin, 5FU With or Without Docetaxel in Patients With T3 and T4 Larynx and Hypopharynx Carcinoma]). The protocol that can best compare with RT alone after ICT is still to be determined.

Objectives: To set out good practice guidelines for locoregional extension assessment of squamous cell carcinoma of the head and neck (excluding nasopharynx, nasal cavities and sinuses)., Materials and Methods: A critical multidisciplinary review of the literature on locoregional extension assessment of squamous cell carcinoma of the head and neck was conducted, applying levels of evidence in line with the French health authority's (HAS) literature analysis guide of January 2000., Conclusion: Based on the levels of evidence of the selected articles and on work-group consensus, graded guidelines are set out for clinical, endoscopic and imaging locoregional extension assessment of head and neck cancer., (Copyright © 2012 Elsevier Masson SAS. All rights reserved.)

Introduction: Micro-anastomosed free fibula flap is an attitude of choice in mandibular defect repair in oncology, enabling effective functional rehabilitation. The present study assessed donor and recipient site morphology and donor-site sequelae., Patients and Methods: The study consecutively recruited patients undergoing mandibular resection with free fibula flap reconstruction in our centre between December 2003 and September 2008. Assessment on adapted scales was performed by two independent expert physicians and patient self-assessment., Results: Out of 49 mandibular reconstructions performed in the centre over the 5-year study period, 23 patients free of recurrence were included. Satisfaction rates were 73% for the recipient site and 70% for the donor-site, with patient/expert agreement of 47% and 49.5% respectively. Donor-site impact was mainly in terms of reduced ankle range of motion (43% of cases) and flexion strength (39%) and discomfort in running (35%) and walking (26%). Risk factors for dissatisfaction were more than 5% weight loss at admission for recipient site dissatisfaction (patient, P=0.012; expert, P=0.046), and skin graft for donor-site dissatisfaction (patient, P=0.04; expert, P=0.035)., Conclusion: Free fibula flap was associated with high satisfaction rates, but non-negligible donor-site impact., (Copyright © 2012 Elsevier Masson SAS. All rights reserved.)

Background: We report the 10-year results of the EORTC trial 24891 comparing a larynx-preservation approach to immediate surgery in hypopharynx and lateral epilarynx squamous cell carcinoma., Material and Methods: Two hundred and two patients were randomized to either the surgical approach (total laryngectomy with partial pharyngectomy and neck dissection, followed by irradiation) or to the chemotherapy arm up to three cycles of induction chemotherapy (cisplatin 100 mg/m(2) day 1 + 5-FU 1000 mg/m(2) day 1-5) followed for complete responders by irradiation and otherwise by conventional treatment. The end points were overall survival [OS, noninferiority: hazard ratio (preservation/surgery) ≤ 1.428, one-sided α = 0.05], progression-free survival (PFS) and survival with a functional larynx (SFL)., Results: At a median follow-up of 10.5 years on 194 eligible patients, disease evolution was seen in 54 and 49 patients in the surgery and chemotherapy arm, respectively, and 81 and 83 patients had died. The 10-year OS rate was 13.8% in the surgery arm and 13.1% in the chemotherapy arm. The 10-year PFS rates were 8.5% and 10.8%, respectively. In the chemotherapy arm, the 10-year SFL rate was 8.7%., Conclusion: This strategy did not compromise disease control or survival (that remained poor) and allowed more than half of the survivors to retain their larynx.

Aim: To define specific staining patterns for the adhesion/growth-regulatory lectin tandem-repeat-type galectin-8 in hypopharyngeal and laryngeal tumor progression and relate these parameters to galectins 1, 3 and 7 in the quest to explore the galectin network., Materials and Methods: The level of expression of galectin-8 was determined immunohistochemically in a series of 18 and 16 cases of tumor-free epithelium, 24 and 10 cases of low-grade dysplasia, 22 and 15 cases of high-grade dysplasia located in peri-tumoral area of 74 and 37 hypopharyngeal and laryngeal carcinomas., Results: Marked upregulation in galectin-8 staining intensity and immunopositive area in malignancy versus dysplasia was seen in hypopharyngeal cancer (p<10(-6)), in laryngeal cancer for labeling index and high-grade dysplasia/carcinoma (p<10(-6)). No correlation to recurrence was delineated., Conclusion: The presented data revealed a divergence within the galectin-1, -3, -7 and -8 network during tumor progression.

Aims: To examine the immunohistochemical expression of helicase-like transcription factor (HLTF) in relation to the prognosis of hypopharyngeal (HSCCs) and laryngeal (LSCCs) squamous cell carcinomas, and to characterize the HLTF protein variants expressed in biopsy specimens of head and neck squamous cell carcinoma (HNSCC) as well as the HeLa cell line., Methods and Results: HLTF expression was determined by immunohistochemistry on a series of 100 hypopharyngeal (stage IV) and 56 laryngeal SCCs (stages I, II and IV). The HLTF variants were defined using reverse transcriptase-polymerase chain reaction and Western blots in 13 fresh HNSCC biopsies and in HeLa cells. High levels of HLTF expression were associated with rapid recurrence rates in a subgroup of 81 stage IV hypopharyngeal SCCs (with complete follow-up). A 95-kDa HLTF variant truncated at the carboxyl-terminal domain was detected in addition to the 115-kDa full-size protein in HNSCC biopsies, while six variants were observed in HeLa cells., Conclusions: Our results demonstrate, for the first time, that hypopharyngeal SCCs presenting high levels of HLTF have a worse prognosis. The quantitative determination of HLTF in hypopharyngeal SCCs was an independent prognostic marker alongside tumour node metastasis staging. HNSCCs expressed the truncated HLTF variant lacking the domains involved in DNA repair.

Background: Both induction chemotherapy followed by irradiation and concurrent chemotherapy and radiotherapy have been reported as valuable alternatives to total laryngectomy in patients with advanced larynx or hypopharynx cancer. We report results of the randomized phase 3 trial 24954 from the European Organization for Research and Treatment of Cancer., Methods: Patients with resectable advanced squamous cell carcinoma of the larynx (tumor stage T3-T4) or hypopharynx (T2-T4), with regional lymph nodes in the neck staged as N0-N2 and with no metastasis, were randomly assigned to treatment in the sequential (or control) or the alternating (or experimental) arm. In the sequential arm, patients with a 50% or more reduction in primary tumor size after two cycles of cisplatin and 5-fluorouracil received another two cycles, followed by radiotherapy (70 Gy total). In the alternating arm, a total of four cycles of cisplatin and 5-fluorouracil (in weeks 1, 4, 7, and 10) were alternated with radiotherapy with 20 Gy during the three 2-week intervals between chemotherapy cycles (60 Gy total). All nonresponders underwent salvage surgery and postoperative radiotherapy. The Kaplan-Meier method was used to obtain time-to-event data., Results: The 450 patients were randomly assigned to treatment (224 to the sequential arm and 226 to the alternating arm). Median follow-up was 6.5 years. Survival with a functional larynx was similar in sequential and alternating arms (hazard ratio of death and/or event = 0.85, 95% confidence interval = 0.68 to 1.06), as were median overall survival (4.4 and 5.1 years, respectively) and median progression-free interval (3.0 and 3.1 years, respectively). Grade 3 or 4 mucositis occurred in 64 (32%) of the 200 patients in the sequential arm who received radiotherapy and in 47 (21%) of the 220 patients in the alternating arm. Late severe edema and/or fibrosis was observed in 32 (16%) patients in the sequential arm and in 25 (11%) in the alternating arm., Conclusions: Larynx preservation, progression-free interval, and overall survival were similar in both arms, as were acute and late toxic effects.

Background: Galectin-1 has been found to modulate lymphocyte invasion in inflammation and to be involved in angiogenesis in models, thus prompting examination of its clinical relevance in laryngeal cancer., Patients and Methods: Immunohistochemical processing of tissue sections (n=53) from patients with stage I/II (n=35) and stage IV (n=18) laryngeal squamous cell carcinoma (LSCC) with a specific anti-galectin-1 antibody and monitoring of CD45/CD31 positivity was combined with quantitative morphometric analysis., Results: Lectin presence in the tumor and endothelial cells was positively correlated, while a negative relationship to the number of CD45-positive lymphocytes was demonstrated. No association was seen with the extent of neovascularization. The mean optical density (MOD) of lectin-dependent staining in the tumor stroma was significantly increased compared to normal stroma., Conclusion: Galectin-1 was not associated with angiogenesis in the studied cohort while galectin-1 in endothelial cells may negatively influence lymphocyte invasion and the mean optical density for the stromal galectin-1 signal is up-regulated in tumors.

The helicase-like transcription factor (HLTF) belongs to the SWI/SNF family of proteins that use the energy from adenosine triphosphate hydrolysis to remodel chromatin during a variety of cellular processes. HLTF is also involved in DNA repair. Using computer-assisted microscopy, the immunohistochemical expression of HLTF was determined using a series of 100 hypopharyngeal and 56 laryngeal squamous cell carcinomas (SCCs) compared to tumor-free epithelia (60 cases) and dysplasias (92 cases). In hypopharyngeal SCC tumor progression, increased HLTF expression was associated with the percentage of immunopositive epithelial tissue areas (p = 0.02) and the staining intensity of the positive area (p = 0.0005). In the cases of laryngeal lesions, the immunolabeling intensity of HLTF significantly decreased with malignancy (p = 0.01). We also observed a significant shift of HLTF expression from the cytoplasm toward the nuclear compartment (p = 0.0007). Our data reveal an association between the presence of HLTF and neoplastic progression of hypopharyngeal and laryngeal SCCs.

Objectives/hypothesis: To examine the level of expression of galectin-3 in relation to neoplastic progression of hypopharyngeal squamous cell carcinomas (HSCCs) and laryngeal squamous cell carcinomas (LSCCs)., Study Design: Retrospective study., Methods: Using a polyclonal antibody against galectin-3 without cross-reactivity to other galectins, we analyzed the presence of galectin-3 using quantitative immunohistochemistry in i) a series of 79 HSCCs compared with 16 normal epithelia, 20 low-grade dysplasia (Low&#95;D) and 25 high-grade dysplasia (High&#95;D) and in ii) a series of 58 LSCCs compared with 34 normal epithelia, 12 Low&#95;D, and 18 High&#95;D. In parallel, galectin-3 expression was studied using Western blotting on a series of 19 fresh biopsies from patients presenting a head and neck tumor., Results: Western blotting excluded a notable degree of proteolytic truncation of galectin-3 in situ. Immunohistochemical galectin-3 positivity expressed as percentage of cells was significantly higher in LSCCs and HSCCs than in Low&#95;D (P = .01) or High&#95;D (P = .0002), respectively. Increased expression of galectin-3 in HSCCs was accompanied by a shift from the cytoplasmic compartment to the nucleus (P = .007). In intertumor-type comparison, laryngeal carcinomas presented nuclear presence of galectin-3 only rarely (1 of 58 cases in laryngeal cancer vs. 27 of 79 cases in hypopharyngeal cancer, P = .00006) and a comparatively low labeling index (P < 10(-6))., Conclusions: Our data reveal an association between level of presence of galectin-3 and neoplastic progression of HSCCs and LSCCs.

Aims: To examine the level of expression of the pleiotropic regulators galectins-1 and -7 in relation to neoplastic progression of hypopharyngeal (HSCCs) and laryngeal (LSCCs) squamous cell carcinomas., Methods and Results: The presence of galectins-1 and -7 was investigated using quantitative immunohistochemistry in (i) a series of 78 HSCCs by comparison with 17 normal epithelia (N&#95;E), 26 low-grade dysplasia (low&#95;D) and 27 high-grade dysplasia (high&#95;D) and (ii) a series of 56 LSCCs by comparison with 50 N&#95;E, 23 low&#95;D and 29 high&#95;D. Galectin-1 positivity expressed as a percentage of cells was significantly higher in carcinomas (HSCCs and LSCCs) than in N&#95;E, low&#95;D or high&#95;D (P < 10(-6)). Galectin-7 expression was elevated in low&#95;D (P = 0.0004) compared with N&#95;E and in carcinomas (HSCC) compared with high&#95;D (P = 0.0002). Tumour progression from high&#95;D to carcinomas was associated with a shift of galectin-1 localization from the nucleus towards the cytoplasm. Increased expression of galectin-7 in dysplasias was accompanied by a shift from the cytoplasmic compartment (N&#95;E) to the nucleus (low&#95;D and high&#95;D)., Conclusions: Our data reveal an association between the level of presence of galectins-1 and -7 and neoplastic progression of HSCCs and LSCCs. Moreover, inverse shifts between nuclear and cytoplasmic positivity intimating functional divergence were detected.

Monitoring of gene-expression profiles is assumed to refine tumor characterization of laryngeal squamous cell carcinomas (LSCCs) with a therapeutic perspective. This is especially expected for adhesion/growth-regulatory effectors such as galectins, a class of endogenous lectins. Using computer-assisted microscopy, we investigated the prognostic value contributed by the quantitative determination of the immunohistochemical levels of expression of galectin-1, -3 and -7 in a series of 62 LSCCs including 42 low- and 20 high-stage LSCCs. As galectin-1 may have a key role leading to a tumor escape from immune surveillance, we also investigated whether or not the level of galectin-1 expression correlated with lymphocyte infiltration in LSCCs. The immunohistochemical determination of expression of galectin-1 is of prognostic value in human squamous laryngeal cancers. LSCCs that display high levels of galectin-1 have worse prognoses than laryngeal cancers with low levels of galectin-1 expression. Elevation of galectin-1 levels in laryngeal cancers can contribute to the process of tumor immune escape by killing the activated T-cells and other protumoral activities such as promoting motility or activity of oncogenic H-Ras proteins. The quantitative determination of galectin-1 in LSCCs is an independent prognostic marker when opposed to TNM staging. It has the potential to identify patients unlikely to benefit from T-cell-mediated immunotherapy, although the definitive effector function from its pro- and antitumoral activity profile has not been delineated.

Objectives: To point out prognosis factors of local recurrence after endoscopic cordectomies for Tis, T1a, T1b, and T2 glottic squamous cell carcinomas., Study Design: A cohort of 110 patients treated from January 1990 to December 2000 at a single institution was retrospectively analyzed: 21 had Tis, 76 T1a, 7 T1b, and 6 T2 (mean follow-up 42 mo; range 1-160 mo)., Methods: The depth and extension of the excision were graded according to the European Laryngological Society Classification. Univariate analysis was used to review the impact on disease-free survival of factors related to the host, the tumor, and the treatment., Results: According to the Kaplan-Meier method, the 5 year overall survival and the disease-free survival were 87% and 75%, respectively. The rates of cause-specific survival, ultimate local control with laser alone, and laryngeal preservation were 97%, 84%, and 90%, respectively. Univariate analysis by the log rank test revealed that vocal muscle infiltration (P = .001) and subglottic involvement (P = .02) have a significant impact on disease-free survival. Of the 22 patients with local recurrence (17 T1a, 1 T1b, and 4 T2), 9 were managed with total laryngectomy, 5 with partial laryngectomy, 4 with further laser cordectomy, 2 with radiotherapy, and 2 had no curative treatment., Conclusion: Transoral laser surgery for early glottic carcinoma is a valid alternative to radiotherapy and partial laryngectomy in terms of oncologic results. It offers low morbidity and excellent retreatment options in case of local failure. Careful patient selection for laser surgery is essential to secure good results.

Aim of the Study: To determine therapeutic and prognostic implications of an associated head and neck primary cancer in patients undergoing oesophagectomy for squamous cell carcinoma of the oesophagus., Patients and Methods: Between 1982 and 2000, 868 patients with oesophageal cancer were operated in our institution, including 78 (9%) who underwent oesophagectomy for associated oesophageal and head and neck cancers; the latter was synchronous (n = 52) or anterior metachronous (n = 26). Influence of head and neck cancer on the treatment of oesophageal carcinoma was analysed retrospectively in terms of surgical therapeutic strategy and survival., Results: Oesophageal resection consisted of oeso-pharyngolaryngectomy (n = 14, 17.9%), subtotal oesophagectomy (n = 62, 79.5%) and cervical oesophagectomy (n = 2, 2.6%). Radical resection (R0) was obtained in 85% of cases. Postoperative mortality rate was 5 % (4/78). Main complications were pulmonary (18% = 14/78) and anastomotic leaks (14% = 11/78), all of them cervical. Follow-up (mean = 25 +/- 27 months) was complete for all 78 patients. Five-year survival after R0 resection was 25%. Survival pronostic factors were denutrition, complete resection, and pT status of oesophageal tumor., Conclusion: In patients with associated carcinomas of oesophagus and head and neck, agressive treatment -including an oesophagectomy- allowed a 5-year survival rate more than 25% without increased mortality or morbidity rates, compared with patients operated on for isolated oesophageal carcinoma.

The aim of this study was to compare the clinical usefulness of ultrasmall superparamagnetic iron oxide (USPIO) MR contrast media (Sinerem, Guerbet Laboratories, Aulnay-sous-Bois, France) with precontrast MRI in the diagnosis of metastatic lymph nodes in patients with head and neck squamous cell carcinoma, using histology as gold standard. Eighty-one previously untreated patients were enrolled in a multicenter phase-III clinical trial. All patients had a noncontrast MR, a Sinerem MR, and surgery within a period of 15 days. The MR exams were analyzed both on site and by two independent radiologists (centralized readers). Correlation between histology and imaging was done per lymph node groups, and per individual lymph nodes when the short axis was > or = 10 mm. For individual lymph nodes, Sinerem MR showed a high sensitivity (> or = 88%) and specificity (> or = 77%). For lymph node groups, the sensitivity was > or = 59% and specificity > or = 81%. False-positive results were partially due to inflammatory nodes; false-negative results from the presence of undetected micrometastases. Errors of interpretation were also related to motion and/or susceptibility artifacts and problems of zone assignment. Sinerem MR had a negative predictive value (NPV) > or = 90% and a positive predictive value (PPV) > or = 51%. The specificity and PPV of Sinerem MR were better than those of precontrast MR. Precontrast MR showed an unexpectedly high sensitivity and NPV which were not increased with Sinerem MR. The potential contribution of Sinerem MR still remains limited by technical problems regarding motion and susceptibility artifacts and spatial resolution. It is also noteworthy that logistical problems, which could reduce the practical value of Sinerem MR, will be minimized in the future since Sinerem MR alone performed as good as the combination of precontrast and Sinerem MR.

Background: Free jejunal transfer has become the standard technique for reconstruction of the pharynx and hypopharynx, especially with proximal neoplastic lesions, whereas gastric tube interposition is the technique of choice for reconstruction of the hypopharynx and cervical esophagus when resection extends below the thoracic inlet., Hypothesis: Surgical ablation is a viable option for advanced hypopharyngeal and cervical esophageal neoplasms, with stomach interposition a safe and preferred method of reconstruction., Design: Retrospective analysis., Setting: University hospital that is a regional referral institution for esophageal cancer treatment and complex digestive reconstructions after esophagectomy., Patients: We reviewed the records of 209 patients who underwent total pharyngolaryngectomy between May 1982 and July 1999. The majority of patients had advanced cancer: hypopharyngeal in 131 cases and cervical esophageal in 78 cases., Interventions: Pharyngolaryngectomy and total esophagectomy with pharyngogastric anastomoses (n = 127); pharyngolaryngectomy, cervical esophagectomy, and reconstruction with free jejunal transplant (n = 77); and pharyngolaryngectomy and total esophagectomy with pharyngocolic anastomoses (n = 5)., Main Outcome Measures: Postoperative mortality and morbidity, long-term survival, and prognostic factors influencing survival., Results: The postoperative in-hospital mortality rate was 4.8% (10 patients), with a postoperative morbidity rate of 38.3%. Alimentary continuity was achieved using the stomach (127 patients), colon (5 patients), or free jejunal autograft (77 patients). The 1-year and 5-year survival rates were 62% and 24%, respectively. There was no significant difference with regard to the survival between gastric transposition and free jejunal autograft, but there were fewer complications in the gastric pull-up group (33% vs 47%, P<.05). The significant adverse factors affecting survival were tumor cervical localization, postoperative complications, disease stages pT3 and pT4 for the cervical esophageal tumors, microscopic pharyngeal penetration, or incomplete resection. The significant beneficial factors were tumor hypopharyngeal localization and postoperative radiotherapy., Conclusions: Surgical ablation is a viable option for advanced hypopharyngeal and cervical esophageal neoplasms, with stomach interposition the preferred method of reconstruction. Although the prognosis is poor, satisfactory short-term palliation can be achieved. The significant adverse factors affecting survival should be taken into account to select the candidates for surgery.

Extended surgical resection of the whole esophagus and associated hypopharynx may require composite reconstructions using a combination of pediculated and free tissue units. Twelve patients were assigned to composite reconstructions of the hypopharynx and esophagus for either metachronous carcinoma of the esophagus and head and neck (group I, n = 4), cervical anastomotic recurrence of esophageal carcinoma (group II, n = 3), or secondary reconstruction after the failure of a previous reconstruction of hypopharynx or esophagus (group III, n = 5). Pediculated tissues were the stomach (n = 10), colon (n = 1), or jejunum (n = 1). A free jejunal graft was constantly interposed between the pharynx and the mobilized organ. There were no hospital deaths. Swallowing function was restored in all patients except one who had cervical leakage as a result of partial necrosis of the free jejunal graft. Composite reconstruction permitted, even in groups I and II in which prognosis was extremely poor, prolonged survival and oral feeding, which proved beneficial in terms of the patients' quality of life.

Transoral laser surgery (TLS) is a safe, time and cost-effective method of treatment for early stage glottic squamous cell carcinoma. This technique is more controversial in case of local extension to other subsite or in case of limited mobility.

The medical charts and operative files of 112 patients (combined inception cohort) with well to moderately differentiated invasive glottic squamous cell carcinoma presenting fixation (22) or impaired motion (90) of the true vocal cord (TVC) consecutively treated with cricohyoidoepiglottopexy (CHEP) at our institutions from 1972 to 1989 were retrospectively reviewed. A minimum 5-year follow-up was always achieved. The Kaplan-Meier 5-year actuarial survival, local recurrence, nodal recurrence, distant metastasis, and metachronous second primary tumor estimate for the entire group of patients were 84.7%, 5.4%, 6.4%, 1.2%, and 10.8%, respectively. The 5-year absolute and cause-specific survival rates were 85.5% and 94.1% for patients with fixation of the TVC and 81.3% and 96% for patients with impaired motion of the TVC. The 5-year actuarial local control rates for patients with fixation or impaired motion of the TVC were 95.4% and 94.4%, respectively. Local recurrence was statistically more likely in patients with positive margins (p = .007). Nodal recurrence was statistically more likely in patients with local recurrence (p = .005). Permanent tracheostomy related to postoperative laryngeal stenosis was requested in 2 patients. Aspiration-related completion total laryngectomy and/or permanent gastrostomy were never requested. Overall, local control and laryngeal preservation were achieved in 97.3%, and 95.5% of patients, respectively. At our institutions, the change from the conservative treatment modalities of radiotherapy and vertical partial laryngectomy to CHEP has brought about an increase in long-term survival, local control, and laryngeal preservation rates when compared to historical controls using vertical partial laryngectomy or radiotherapy.

The free jejunal graft is a very useful procedure for hypopharyngeal reconstruction after total pharyngolaryngectomy. Between 1985 and 1994 56 patients with squamous cell carcinoma of the hypopharynx were treated by this method. The median age was 54 (range 35-76). There were 54 men and 2 women. The mortality rate was 4% (2/56). The graft failure was 4% (2/56). Good swallowing function was achieved in 91% (49/54 assessable patients). Nine patients developed local recurrences, four patients had local and neck recurrences. Distant metastases occurred in six patients and five developed metachronous cancers. Follow-up analysis showed a 5-yr survival rate of 33%. After 10 yr, the free jejunal graft has become, for us, the method of choice for hypopharyngeal reconstruction after total pharyngolaryngectomy.

Background: Supraglottic hemilaryngopharyngectomy is a functional procedure suitable for the treatment of carcinoma of the upper part of the pyriform sinus and carcinoma of the lateral laryngeal margin. It consists of resection of the supraglottic hemilarynx and ipsilateral pyriform sinus., Methods: Forty-nine patients underwent this procedure from 1979 through 1994. The median age was 51 (40-72). The data were collected by a review of patients' records., Results: Two patients died in the postoperative period. The average time of removal of the nasogastric tube was 14 days. The survival rate at 3 years was 52% and at 5 years, 47%. The local recurrence rate was 2%, the overall neck recurrence was 15%, metastasis occurred in 15% of cases., Conclusions: Indications for this procedure are carcinoma of the upper part of the pyriform sinus and carcinoma of the laryngeal margin with normal vocal cord mobility.

Background: As a general rule, surgery whenever possible, followed by irradiation is considered to be the standard treatment for cancer of the hypopharynx, thus sacrificing natural speech. In most patients, surgery includes removal of the larynx., Purpose: A prospective, randomized phase III study was conducted by the European Organization for Research and Treatment of Cancer (EORTC) starting in 1990 to compare a larynx-preserving treatment (induction chemotherapy plus definitive, radiation therapy in patients who showed a complete response or surgery in those who did not respond) with conventional treatment (total laryngectomy with partial pharyngectomy, radical neck dissection, and postoperative irradiation) in previously untreated and operable patients with histologically proven squamous cell carcinomas of the pyriform sinus or aryepiglottic fold, but free of other cancers., Methods: Patients were randomly assigned to one of two treatment arms: 1) immediate surgery with postoperative radiotherapy (50-70 Gy) or 2) induction chemotherapy (cisplatin [100 mg/m2] given as a bolus intravenous injection on day 1, followed by infusion of fluorouracil [1000 mg/m2 per day] on days 1-5). An endoscopic evaluation was performed after each cycle of chemotherapy. After two cycles, only partial and complete responders received a third cycle. Patients with a complete response after two or three cycles of chemotherapy were treated thereafter by irradiation (70 Gy); nonresponding patients underwent conventional surgery with postoperative radiation (50-70 Gy). Salvage surgery was also performed when patients relapsed after chemotherapy and irradiation. The trial was designed to test the equivalence of the two treatment arms; i.e., the induction chemotherapy treatment would be judged equivalent to immediate surgery if the relative risk of death for induction chemotherapy compared with immediate surgery was significantly less than 1.43 using a one-sided hypothesis test at the .05 level of significance., Results: Two hundred two patients entered the trial and were randomly assigned; only 194 were eligible for treatment (94 in the immediate-surgery arm and 100 in the induction-chemotherapy arm). In the induction-chemotherapy arm, complete response was seen in 52 (54%) of 97 patients with local disease (primary tumor) and in 31 (51%) of 61 patients with regional disease (involvement of the neck). Treatment failures at local, regional, and second primary sites occurred at approximately the same frequencies in the immediate-surgery arm (12%, 19%, and 16%, respectively) and in the induction-chemotherapy arm (17%, 23%, and 13%, respectively). In contrast, there were fewer failures at distant sites in the induction-chemotherapy arm than in the immediate-surgery arm (25% versus 36%, respectively; P = .041). The median duration of survival was 25 months in the immediate-surgery arm and 44 months in the induction-chemotherapy arm and, since the observed hazard ratio was 0.86 (logrank test, P = .006), which was significantly less than 1.43, the two treatments were judged to be equivalent. The 3- and 5-year estimates of retaining a functional larynx in patients treated in the induction-chemotherapy arm were 42% (95% confidence interval = 31%-53%) and 35% (95% confidence interval = 22%-48%), respectively., Conclusions and Implications: Larynx preservation without jeopardizing survival appears feasible in patients with cancer of the hypopharynx. On the basis of these observations, the EORTC has now accepted the use of induction chemotherapy followed by radiation as the new standard treatment in its future phase III larynx preservation trials.

The frequency of lung cancers associated with synchronous head and neck malignancies can be evaluated between 1.5 to 2%. The purpose of our work was to determine if complete endoscopic head and neck examination performed under general anesthesia was superior than clinical head and neck examination for the diagnosis of these synchronous additional tumors. From july 1991 to august 1992, we realised a prospective study on 58 consecutive patients suffering from pulmonary removable lung cancers. All the patients had a clinical head and neck examination during the preoperative period. Immediately before thoracotomy a complete endoscopy of head and neck aerian and digestive tract was performed. During this last examination 18 new macroscopical lesions were discovered in 13 patients: benign lesions (n = 17), oral cavity and laryngeal dysplasia (n = 1). The one gingivolingual sulcus carcinoma, already discovered by the clinical examination, was confirmed. This study suggests that complete head and neck endoscopy is not superior than clinical examination for the diagnosis of synchronous malignancies before lung cancers removal.

Background: Subtotal laryngectomy with cricohyoidopexy is a functional laryngectomy suitable for treatment of supraglottic carcinomas. This procedure consists of resection of the thyroid cartilage, the paraglottic space, the epiglottis, and the entire pre-epiglottic space. The cricoid cartilage, the hyoid bone, and at least one arytenoid cartilage are spared., Methods: Between 1973 and 1990, we used subtotal laryngectomy with cricohyoidopexy to treat 61 successive patients with supraglottic carcinomas. The data were collected by a review of patient records. The cancers were stages T1 (2), T2 (41), T3 (14), and T4 (4), according to the 1979 American Joint Committee on Cancer staging criteria., Results: No patient died postoperatively. Forty-nine (80%) were able to eat normally before the 28th day. A follow-up analysis showed survival rates of 83% at 3 years and 79% at 5 years., Conclusion: We propose subtotal laryngectomy with cricohyoidopexy for the surgical treatment of supraglottic carcinomas extending to the true vocal cord, the ventricle, and the posterior third of the false vocal cord.

57 patients with cancer of the hypopharynx underwent 59 pharyngo-esophageal reconstructions with a free jejunal graft after total removal of a tumor combined with resection of the circumferential tissues. 18 patients had been previously irradiated. Median resumption of oral intake was 16 days; 40 out of 50 patients (98%) followed for more than 2 years regained normal eating habits. The cumulative 5-year survival rate was 44%. The free jejunal graft should be advocated as a safe and reliable procedure for hypopharyngeal cancer.

We first described subtotal laryngectomy with crico-hyoido-epiglotto-pexy in 1974. This procedure is a modification of Majer's operation and results in the complete resection of the intact thyroid cartilage. The epiglottic petiole, the false cords, the true cords, and one arytenoid are also excised, along with the paraglottic space. The pharynx is closed by suturing the cricoid to the epiglottis and the hyoid bone. The neoglottis is occluded during deglutition by the epiglottis and the base of tongue, which come into contact with the remaining arytenoid. Postoperative hospitalization lasts approximately 3 weeks, and patients have a strong but deep voice. Between 1972 and 1985, we treated 104 patients with stage T2 and T3 lesions of the glottis using this method. A retrospective analysis showed that the overall survival rate of patients was 86% at 3 years and 75% at 5 years. Five patients experienced local recurrence. Seven patients had recurrences in the neck, and eight developed second primaries. Thirteen patients were lost to follow-up or developed intercurrent disease. Patients with T3NO lesions were treated with unilateral prophylactic neck dissection, and positive nodes were found in 23% of cases. We believe that the high proportion of positive nodes justifies routine prophylactic neck dissection in these patients. Because our operation is associated with good local control (5% recurrence rate), we propose that, for the treatment of extended glottic cancers, it replace transcartilaginous procedures that are associated with much higher recurrence rates.

From 1980 to 1987, 37 patients were operated with a reconstructive anterior frontal laryngectomy including epiglottoplasty such as described by Tucker. These patients presented with epidermoid carcinomas of the glottis. The carcinological results are satisfactory, with a survival rate of 33 of 37 patients at 3 years and 22 of 25 patients at 5 years. However, the control of the paraglottic space still is insufficient after this type of surgery, and we reserve it for the tumors confined to the glottic level, without impairment of mobility. The anterior frontal laryngectomy performed is extensive and frontolateral. It is used for a few of its former indications, as showed by the comparison of the periods before and after 1980.