Pharyngolaryngeal Carcinomas Research Articles

Management of the irradiated N0-neck during salvage pharyngo-laryngeal surgery

BackgroundSalvage surgeries are challenging procedures, with an associated poor prognosis. Management of the N0 neck in those situations remains controversial. We aim to compare oncologic outcomes regarding neck management after surgery for N0 pharyngo-laryngeal carcinoma occurring after loco-regional radiotherapy. MethodsWe conducted a multicentric retrospective study, including all patients undergoing surgery for persistent, recurrent or new primary N0 carcinoma of the oropharynx, hypopharynx or larynx between 2005 and 2015, following loco-regional radiotherapy. ResultsA total of 239 patients were included, concerning respectively 44%, 34% and 22% oropharyngeal, laryngeal and hypopharyngeal tumors operated. A neck dissection was performed in 143 patients (60%), with an occult nodal metastasis rate of 9%. This rate was higher for hypopharyngeal carcinomas (18%, p = 0.16) and tumors with initial nodal involvement (16%, p = 0.05). With a median follow-up of 60 months, the median overall survival (OS) and progression-free survival rates (PFS) were 34 months and 25 months. We identified negative margin excision status, age at the time of surgery (under 60) and delay between RT and surgery over 2 years as the only variables associated with better OS (p < 0.0001 and p = 0.004) and PFS (p < 0.0001 and p = 0.010) in multivariable analysis, with no difference regarding neck management. Regional progression (alone or with distant metastasis) was noted in 10 cases: 4 in the neck observation group (4%) versus 6 in the neck dissection group (4%). ConclusionElective lymph node dissection of irradiated neck should not be routinely performed in patients undergoing surgery for persistent, recurrent or new primary pharyngo-laryngeal carcinomas

Association between Helicobacter pylori and Pharyngolaryngeal Carcinomas: The Role in the Development and Prognostic Significance

Association between Helicobacter pylori and Pharyngolaryngeal Carcinomas: The Role in the Development and Prognostic Significance

Importanţa utilizării alimentaţiei prin gastrostomă endoscopică percutanată în managementul pacienţilor cu neoplasme ale capului şi gâtului

Background. Nowadays the newest method of nutrition in patients with head and neck carcinomas is the use of percutaneous endoscopic gastrostomy. Aim. Since 2012 we have actively implemented the use of Nutrison administered on PEG before and after the surgical removal of laryngeal or pharyngolaryngeal carcinomas. Material and method. We conducted a prospective descriptive study on 54 cases that benefited from prophylactic PEG placement. Results. Among the cases included in our study 28 underwent total laryngectomy with bilateral removal of lymph nodes, 23 patients required pharyngo-laryngectomy, 2 cases presented invading tonsilar carcinomas and 1 case with esophageal neoplasm received PEG for palliative purpose. Conclusions. The use of PEG is cost efficient lowering the number of in hospital stay days, permits the treatment of complex cases with multiple comorbidities and actively prevents the development of pharyngocutaneous fistulae.

Abstract A66: Galectin-1 expression correlated with mesenchymal differentiation and resistance to chemotherapy in carcinoma cells

Abstract Background: Galectin-1, a multifunctional lectin regulating various aspects of tumorigenesis such cell migration and invasiveness, has been involved in cancer cells chemoresistance and in metastasis induction. Epithelial-to-mesenchymal transition (EMT) also allows carcinoma cells to acquire invasive properties and resistance to chemotherapy. The aim of the study is to evaluate galectin-1 and EMT markers as predictive biomarkers of chemoresistance in human cancer. Material and Methods: The antiproliferative effects (IC50) of 5-fluorouracil and docetaxel were evaluated by MTT assay and mRNA expressions of galectin-1, vimentin, N-cadherin, SNAIL, SLUG, ZEB1, TWIST, E-cadherin, claudin-4, keratin-8 and -18 by qRT-PCR in a panel of 11 human cancer cell lines. Galectin-1, vimentin, E-cadherin protein expressions were analyzed by immunohistochemistry in tumor biopsies (prior to chemotherapy) from patients with locally advanced pharyngolaryngeal carcinomas subsequently treated with an induction chemotherapy combining cisplatin, 5fluorouracil, and docetaxel as part of an organ preservation program. Protein expressions was quantified in responders (&amp;gt;50% reduction in tumor size on CT-scan or MRI) and compared to non-responders (&amp;lt;50% reduction in tumor size on CT-scan or MRI) to chemotherapy. Results: In our panel of human cancer cells, mRNA expression of galectin-1 was correlated with resistance to docetaxel (R2=0.617, p-value=0.04). Higher mRNA expression of galectin-1 was also correlated with higher expression of mesenchymal marker vimentin (R2=0.308, p-value=0.02) and lower expression of epithelial markers such as E-cadherin (R2=0.461, p-value=0.02), keratin-8 (R2=0.493, p-value=0.02) and keratin-18 (R2=0.382, p-value=0.04). Cancer cells displaying higher mRNA levels of mesenchymal markers such as vimentin, N-cadherin, SNAIL, ZEB1, and TWIST and lower levels of epithelial markers as E-cadherin, claudin-4 and keratin-8 and -18 were more resistant to 5-fluorouracil and docetaxel. Galectin-1, vimentin and E-cadherin protein-expressions were evaluated in biopsies patients with squamous cell carcinoma prior to chemotherapy. Galectin-1 positive staining was more frequently observed in non-responder compared to responder patients. Interestingly, galectin-1 was preferentially expressed in the nucleus of cancer cells in responders whereas in non-responders, galectin-1 was mainly found in the stroma. Resistance to chemotherapy was also more frequently observed in tumors with mesenchymal differentiation. A decreased E-cadherin and an increased vimentin expression were observed in non-responder compared to responder patients (p&amp;lt;0.05). Conclusion: High galectin-1 expression correlated with EMT differentiation of cancer cells and was associated with resistance to several cytotoxic agents. Targeting galectin-1 should be evaluated to counteract resistance to chemotherapies.

Abstract 728: CXCL12 (SDF-1) chemokine expression as a baseline factor associated with resistance to induction chemotherapy in head and neck squamous cell carcinoma

Abstract Background. SDF-1, and its cognate receptor CXCR4, are recognized as major factors in tumor progression and metastasis. Recent data also suggest that chemokines may play a role in resistance to chemotherapy. In this study, we investigated the expression of SDF-1 and CXCR4 in initial tumor biopsies prior to treatment in patients treated by induction chemotherapy for organ preservation and correlated this expression with response to chemotherapy. Material and Methods. Patients with locally advanced pharyngo-laryngeal carcinomas, candidates for neoadjuvant platinum-based chemotherapy as part of an organ preservation program, were considered for this study. Objective response in organ preservation accounted for more than 50% reduction in tumor size on CT-scan or MRI. Tissue biopsies were scored for SDF-1, CXCR4, Vimentin and E-cadherin staining by immunohistochemistry. Staining was measured according to a specific scoring scale. Biopsies were all read by three different observers for scoring adjudication and quantification was performed using the Histolab Software (Microvision). Results. Among the 42 patients who entered in this study, 23 had primary site in the hypopharynx and 19 in the larynx. Twenty-two patients experienced objective response and 20 patients were non-responders to induction chemotherapy. SDF-1 staining score was higher in cancer cells than that in normal epithelial cells located in the close vicinity of the tumor. SDF-1 staining was predominantly located in the cytoplasm of cancer cells. The level of SDF-1 expression was significantly higher in tumors from non-responders compared to responders (score: 155 vs 110, p=0.01). CXCR4 expression was similar between responders and non-responders, and predominantly located in the cytoplasm and the nucleus of cancer cells. Vimentin and E-cadherin were evaluated as potential differentiation markers. Few tumor cells expressed Vimentin in our biopsies. Interestingly lower E-cadherin expression was observed in non-responders compared to responders (score: 110 vs 170, p=0.01) suggesting that loss in epithelial differentiation may facilitate resistance to chemotherapy in this population. Conclusion. High expression levels of SDF-1 cytokine and the loss of E-cadherin as a marker of epithelial differentiation in cancer cells were shown to correlate with the lack of response to induction chemotherapy in hypopharyngeal and laryngeal squamous cell carcinomas. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 728. doi:1538-7445.AM2012-728

Using polymerase chain reaction to human papillomavirus in oral and pharyngolaryngeal carcinomas

Purpose: Increasingly, evidence has shown that human papillomavirus (HPV) plays a role in the induction of certain carcinomas. The presence of HPV sequences in 56 previously untreated oral and pharyngolaryngeal carcinomas was examined by the polymerase chain reaction (PCR). Materials and Methods: After DNA extraction, samples underwent 40 replication cycles with specific oligonucleotide primers corresponding to sequences from the E6 open-reading frame of HPV-6b, HPV-16, and HPV-18. To determine the E6 genomic integration, positive samples were processed with specific primers for the corresponding HPV L1 genes. Genomic HPV DNA cloned into PBR 322 was used as positive control. Results: HPV E6 DNA of the 6b and 16 types was detected in 14 patients (25%). The L1 gene was not present. Conclusion: Detected HPV E6 DNA might be integrated into the cell genome in the positive cases as indicated by the absence of the L1 gene-coding for the viral capside. Histological and clinical parameters, such as tumor location, degree of differentiation, stage, recurrence, and survival rates, were unrelated to the presence of HPV.

The "gregorio marañon" hospital experience in the treatment of laryngeal carcinoma.

A retrospective analysis has been carried out of 4100 patients with pharyngolaryngeal carcinoma who were seen at the Hospital Gregorio Marañon between 1962 and 1993. 1287 patients were excluded from this study, leaving 2813 patients available for analysis. The great majority of the 2813 pharyngolaryngeal carcinomas were primary laryngeal tumours (2519). These are the subject of our study.We present our theoretic protocol for treatment of laryngeal carcinoma, both glottic and supraglottic, with special attention to the partial surgery. Our oncological and functional results are presented and discussed.

Response to chemotherapy as justification for modification of the therapeutic strategy for pharyngolaryngeal carcinomas

From September 1983 to September 1987, 238 patients with squamous cell carcinoma of the upper aerodigestive tract were given 3 cycles of chemotherapy [cisplatinum (cis-DDP), 100 mg/m2 on day 1; 5-fluorouracil (5-FU), 1,000 mg/m2 on days 2-6] before any local treatment. Eighty-one of these patients had pharyngolaryngeal cancer. Of the 45 of 50 laryngeal cancers and 26 of 31 hypopharyngeal cancers suitable for evaluation, complete responses (CR) were obtained in 51.1% and 53.8%, respectively. These response rates led to changes in the postchemotherapy protocols. For CRs, multilating surgical protocols were replaced by definitive radiotherapy: one local recurrence has been observed among the 9 laryngeal cancers, and 3 of 10 hypopharyngeal cancer patients, who had an initial indication of total laryngectomy or total pharyngolaryngectomy replaced by radiotherapy. In the group of CR, survival rates at 2 years were 93% and 69%, respectively, for the larynx and hypopharynx vs 65.6% and 40% for non-CR patients. The possibility of conservative treatment sparing vocal function with a high degree of reliability would in itself appear to be justification for induction chemotherapy in pharyngolaryngeal cancers, even though its long-term effects remain controversial.