Total Laryngectomy with Horizontal Mechanical Closure of the Pharyngoesophagectomy: Evaluation of the Effectiveness in Elderly Patients

Abstract Introduction The main modalities of surgical treatment for laryngeal cancer include transoral laser microsurgery (TLM), open preservation surgery, and total laryngectomy (TL). In the elderly, for the presence of comorbidities, the surgical approach more appropriate in many cases remains TL. The use of a stapler for the closure of the esophagus has been introduced to reduce surgical time and postoperative complications such as pharyngocutaneous fistula (PCF). Objective In the present study, we have evaluated the effectiveness of the use of the horizontal mechanical pharyngoesophageal closure in patients who underwent TL. Methods This nonrandomized study was performed on consecutive patients with histopathologically proven squamous cell endolaryngeal carcinoma. The TLwas performed using a linear stapler to mechanically suture the pharyngotomy using the semiclosed technique. Results A total of 33 patients underwent TL, and 13 of themunderwent neck dissection. A total of 15 patients (45.4%) were ≤70 years old, and 18 were > 70 years old. Analyzing the results in relation to age, patients > 70 years old showed tumors at an earlier stage than those aged ≤70 years old. Furthermore, in this group there was a greater number of patients who had comorbidities (p = 0.014). In total, we had 2 (6%) cases of PCF in 6.6% in the group ≤70 years old, and in 5.5% of the group > 70 years old (p = 1.00). Conclusions The use of the stapler for the horizontal closure of the pharyngoesophagectomy in the patients subjected to TL is proven to be useful and safe even when used in elderly patients.

Total Laryngectomy with Horizontal Mechanical Closure of the Pharyngoesophagectomy: Evaluation of the Effectiveness in Elderly Patients.

Introduction The main modalities of surgical treatment for laryngeal cancer include transoral laser microsurgery (TLM), open preservation surgery, and total laryngectomy (TL). In the elderly, for the presence of comorbidities, the surgical approach more appropriate in many cases remains TL. The use of a stapler for the closure of the esophagus has been introduced to reduce surgical time and postoperative complications such as pharyngocutaneous fistula (PCF). Objective In the present study, we have evaluated the effectiveness of the use of the horizontal mechanical pharyngoesophageal closure in patients who underwent TL. Methods This nonrandomized study was performed on consecutive patients with histopathologically proven squamous cell endolaryngeal carcinoma. The TL was performed using a linear stapler to mechanically suture the pharyngotomy using the semiclosed technique. Results A total of 33 patients underwent TL, and 13 of them underwent neck dissection. A total of 15 patients (45.4%) were ≤70 years old, and 18 were > 70 years old. Analyzing the results in relation to age, patients > 70 years old showed tumors at an earlier stage than those aged ≤70 years old. Furthermore, in this group there was a greater number of patients who had comorbidities ( p = 0.014). In total, we had 2 (6%) cases of PCF in 6.6% in the group ≤70 years old, and in 5.5% of the group > 70 years old ( p = 1.00). Conclusions The use of the stapler for the horizontal closure of the pharyngoesophagectomy in the patients subjected to TL is proven to be useful and safe even when used in elderly patients.

Videolaryngoscopy during Conscious Sedation in Patients Not Suitable for Phonosurgery by Microlaryngoscopy: A Pilot Study.

BACKGROUND: Microlaryngoscopy is the preferred and most widely used technique in phonosurgery for the treatment of benign and early malignant glottic lesions. However, the procedure may be technically difficult or impossible due to alterations of the cervical spine that may not allow hyperextension of the head or may present general anesthesia contraindications. The aim of this study is to evaluate the efficacy and safety of our surgical approach for lesions of the vocal folds in patients who are not suitable for phonosurgery by microlaryngoscopy. This approach applies videolaryngoscopy during conscious sedation, which combines local anesthesia with moderate analgosedation by using midazolam and fentanyl with premedication. METHODS: A total of 235 patients affected by benign diseases or suspicious cancerous lesions of the vocal folds were retrospectively evaluated. RESULTS: The method has shown a success rate of 95.5, 89, 52.3, and 86.7% in cases of polyps of the vocal folds, Reinke's edema, cysts of the vocal folds, and suspicious lesions of the larynx, respectively. Only 3 patients (1.27%) have been reported to experience adverse events. CONCLUSION: The results suggest that the method is an effective and safe procedure without relevant local and/or general complications.

Electronic Cigarette: Role in the Primary Prevention of Oral Cavity Cancer.

BACKGROUND: Cigarette smoke has been identified as the main cause of oral cavity carcinoma. Recently, the electronic cigarette, a battery-operated device, was developed to help smokers stop their tobacco addiction. This study aimed to evaluate the safety of electronic cigarettes and to establish the possible role of such device in the primary prevention of oral cavity cancer. SUBJECTS AND METHODS: This study included 65 subjects who were divided into three groups (smokers, e-cigarette smokers, and nonsmokers). All subjects were submitted to cytologic examination by scraping of oral mucosa. The slides were microscopically evaluated through a micronucleus assay test. RESULTS: The prevalence of micronuclei was significantly decreased in the e-cigarette smoker group. There were no statistically significant differences in micronuclei distribution according to the type of cigarette, gender, and age. CONCLUSIONS: The use of electronic cigarettes seems to be safe for oral cells and should be suggested as an aid to smoking cessation.

Connexin 43 (Cx43) Expression in Laryngeal Squamous Cell Carcinomas: Preliminary Data on Its Possible Prognostic Role.

The aim of the report is to evaluate the prognostic and predictive role of Connexin 43 (Cx43) expression in laryngeal squamous cell carcinomas. Eighty-seven previously untreated patients submitted to laryngectomy ± neck dissection ± radiotherapy were enrolled in this retrospective study. The original primary tumor slides were reassessed, tumor grade and stage reviewed, and Cx43 immunohistochemical analysis performed: only cytoplasmic membranous staining of Cx43 has been shown. Neither significant correlation has been showed for clinical T (p = 0.75) and N (p = 0.81), while significant correlation has been found with grading (p < 0.0001) and pathological N (p < 0.0001). Five year overall survival (OS) of the 87 patients was 54 %; 5 year OS was 59.6 % in Cx43 positive patients and 37.1 % in Cx43 negative patients, but also this difference did not reach statistical significance (p = 0.058). Our best findings were: poorly differentiated carcinomas had low or negative Cx43 expression; moderately differentiated tumors without node metastasis and no radiotherapy but with Cx43 expression had a better outcome; moderately differentiated tumors without node metastasis and no radiotherapy but without Cx43 expression had a worse outcome; moderately differentiated tumors with node metastasis and radiotherapy but without Cx43 expression had a better outcome. Interestingly, in G2 head and neck squamous cell carcinomas with lymph node metastasis at the time of diagnosis, Cx43 aberrant overexpression could identify a subset of patients with poor prognosis, far less responsive to radio/chemotherapy.

Electrochemotherapy in combination with chemoradiotherapy in the treatment of oral carcinomas in advanced stages of disease: efficacy, safety, and clinical outcomes in a small number of selected cases.

INTRODUCTION: Electrochemotherapy (ECT) is a new therapeutic method that is used in oncology as palliative treatment in patients with recurrent head and neck tumors and who are not candidates for standard therapeutic options. The aim of our study was to evaluate the cytoreductive effect of ECT in patients subjected to chemoradiotherapy for squamous cell carcinoma of the oral cavity. The primary endpoint of the study was to verify tumor debulking after ECT treatment as neoadjuvant, before conventional chemoradiotherapy. The secondary endpoint was to assess the safety and tolerability of ECT treatment. MATERIALS AND METHODS: This experimental study was conducted at the Division of Otolaryngology, University of Catanzaro, Italy. From February 2013 to February 2014, four patients were enrolled, two males and two females, with a mean age of 56 years (range: 47-65 years), and with squamous cell carcinoma of the oral cavity in advanced stages of disease (T3-T4). All patients, with their informed consent, received ECT treatment in accordance with the Standard Operating Procedures defined in the European Standard Operating Procedures on Electrochemotherapy (ESOPE) study, followed by conventional chemoradiotherapy. Their response to ECT treatment was assessed after 30 days. For each patient, the following parameters were evaluated with the appropriate forms: local tumor control, control of pain (analgesia postsurgery scale [APS]), and quality of life (Short Form [36] Health Survey [SF-36]; v1). RESULTS: Three of four patients (75%) showed a partial response, whereas in one patient (25%), the disease remained stable. The treatment was well-tolerated by all patients, according to the APS and SF-36 results. CONCLUSION: Although the study was conducted on a small number of cases, data from this study show that ECT represents a safe and effective treatment in terms of tumor cytoreduction and locoregional control of the disease. It also allows good control of postoperative pain and short hospitalization.

Early glottic cancer: role of MRI in the preoperative staging.

INTRODUCTION: Clinical staging is the most important time in management of glottic cancer in early stage (I-II). We have conducted a prospective study to evaluate if magnetic resonance imaging (MRI) is more accurate than computed tomography (CT) about tumoral extension, to exactly choose the most appropriate surgical approach, from organ preservation surgery to demolitive surgery. MATERIALS and METHODS: This prospective study was conducted on 26 male patients, with suspected laryngeal neoplasia of glottic region. The images of MRI and CT were analyzed to define the expansion of glottic lesion to anterior commissure, laryngeal cartilages, subglottic and/or supraglottic site, and paraglottic space. The results of MRI and CT were compared with each other and with the pathology report. RESULTS: CT accuracy was 70% with low sensitivity but with high specific value. MRI showed a diagnostic accuracy in 80% of cases, with a sensitivity of 100% and high specificity. Statistical analysis showed that MRI has higher correlation than CT with the pathology report. CONCLUSION: Our study showed that MRI is more sensitive than CT in the preoperative staging of early glottic cancer, to select exactly the eligible patients in conservative surgery of the larynx, as supracricoid laryngectomy and cordectomy by CO2 laser.

The role of BMI1 as a biomarker of cancer stem cells in head and neck cancer: a review.

Emerging studies show that BMI1 (B cell-specific Moloney murine leukemia virus integration site 1) has an important function as a biomarker of cancer stem cells (CSCs), i.e. cells with self-renewal characteristics, capable of tumor initiation, progression, invasion, metastasis, tumor recurrence and resistance to chemotherapy and radiotherapy. The failure of current anticancer therapies can be attributed to the relative ineffectiveness of drug and radiation treatments on CSCs, thereby preserving the full capacity of the cells to reproduce tumors. The development of new strategies is currently hindered by the lack of reliable markers for the identification of these CSCs. At present, they have been isolated from solid tumors at various locations using a variety of surface markers, including CD34, CD133, CD24, CD44, CD29 and CD31, in addition to the methods of isolation and cell culture via the Wnt, BMI1, Notch and Hedgehog pathways. The discovery of specific tumor targets for CSCs would constitute a big step in the research for the definitive therapy against cancer. More studies are being conducted that consider the role of CSCs in head and neck cancers with potential for an impact on clinical-surgical outcomes from the knowledge that is being gained. A promising intracellular marker of CSCs in head and neck cancer is the oncoprotein BMI1, with specific data about its prognostic value based on the specific location.

Prognostic role of salivary CD44sol levels in the follow-up of laryngeal carcinomas.

BACKGROUND: The purpose of this study was to verify CD44sol levels in the saliva of patients during follow-up after surgery for laryngeal cancer, to compare them with those registered at the time of diagnosis (pre-intervention) in the same patients, and to assess the reliability of the test as a prognostic indicator. METHODS: This prospective study was performed on 21 patients having laryngeal cancer who underwent surgery at the Division of Otolaryngology, University of Catanzaro; twelve adults with head and neck benign disease were recruited to form a control group. For each patient, the clinical­anamnestic data were collected and entered into a database. The sampling of undiluted saliva was performed the day before surgery and during the follow-up, every 3 months. Salivary CD44sol levels were determined using the ELISA method. RESULTS: Mean salivary CD44sol levels in the patients group before surgery (pre-intervention) were significantly higher than those in the control group (70.75 ± 33.8 vs. 12.4 ± 8.7 ng/ml). At follow-up performed 3 months after surgery, 18 of 21 (85.71%) patients had a reduction in salivary CD44sol levels, with a mean value of 50.1 ng/ml; the difference between these and pre-intervention CD44sol levels was statistically significant (P < 0.04). Mean CD44sol levels of 31.1 ng/ml at 6 months post-intervention have been determined in 19 of 21 enrolled patients; none of the 19 patients have actual signs of recurrence. CONCLUSIONS: These data seem to show that the determination of salivary CD44sol levels can represent a promising prognostic test in laryngeal carcinomas.

Effectiveness of therapeutic selective neck dissection in laryngeal cancer.

BACKGROUND: The aim of this study was to evaluate the effectiveness of selective neck dissection (SND) in patients with laryngeal cancer and clinically positive cervical nodes. SUBJECTS AND METHODS: A retrospective review of the clinical records of 58 consecutive untreated patients affected by laryngeal carcinoma and submitted to surgical treatment was performed. RESULTS: Twenty-six (44.8%) patients received monolateral neck dissection and 32 (55.2%) bilateral neck dissection. A total of 90 hemineck dissections were performed. Histopathological examination revealed that 25 of the 58 patients had negative nodes (pN0) and 33 had positive nodes (pN+). Extracapsular spread was found in 12 of the 33 pN+ patients. Twenty-eight of the 58 (48.2%) patients were submitted to adjuvant radiotherapy. Six of the 58 patients submitted to neck dissection had neck recurrence (rate of 10.3%). The only independent prognostic factor for neck recurrence was extracapsular spread. For the 58 patients, the 5-year overall survival was 50% and the disease-specific survival 68.9%. The 5-year disease-specific survival was 76% for pN0 patients and 63.6% for pN+ patients. CONCLUSIONS: SND can represent a therapeutic procedure because it has shown oncological results comparable to those of comprehensive neck dissection, especially when SND is combined with adjuvant radiotherapy.

Cancer stem cells in head and neck cancer.

Cancer stem cells (CSCs), also called "cells that start the tumor," represent in themselves one of the most topical and controversial issues in the field of cancer research. Tumor stem cells are able to self-propagate in vitro (self-renewal), giving rise both to other tumor stem cells and most advanced cells in the line of differentiation (asymmetric division). A final characteristic is tumorigenicity, a fundamental property, which outlines the tumor stem cell as the only cell able to initiate the formation of a tumor when implanted in immune-deficient mice. The hypothesis of a hierarchical organization of tumor cells dates back more than 40 years, but only in 1997, thanks to the work of John Dick and Dominique Bonnet, was there the formal proof of such an organization in acute myeloid leukemia. Following this, many other research groups were able to isolate CSCs, by appropriate selection markers, in various malignancies, such as breast, brain, colon, pancreas, and liver cancers and in melanoma. To date, however, it is not possible to isolate stem cells from all types of neoplasia, particularly in solid tumors. From a therapeutic point of view, the concept of tumor stem cells implies a complete revision of conventional antineoplastic treatment. Conventional cytotoxic agents are designed to target actively proliferating cells. In the majority of cases, this is not sufficient to eliminate the CSCs, which thanks to their reduced proliferative activity and/or the presence of proteins capable of extruding chemotherapeutics from the cell are not targeted. Therefore, the theory of cancer stem cells can pose new paradigms in terms of cancer treatment. Potential approaches, even in the very early experimental stages, relate to the selective inhibition of pathways connected with self-renewal, or more specifically based on the presence of specific surface markers for selective cytotoxic agent vehicles. Finally, some research groups are trying to induce these cells to differentiate, thus making them easier to remove. For all these reasons, we have collected existing literature on head and neck cancer stem cells that correlate the biological characteristics of this subpopulation of cancer cells with the clinical behavior of tumors.

Role of CD44 as a marker of cancer stem cells in head and neck cancer.

In recent years, many studies have shown that some types of tumors are characterized by the presence of cells with stem-like characteristics, called cancer stem cells (CSCs). These are considered cells that initiate the tumor and are probably responsible for tumor recurrence. CSCs have the capacity for self-renewal, the potential to give rise to one or more cell types within the tumor, and the ability to drive, in a continuous manner, the proliferation of malignant cells. The failure of current cancer therapies can be attributed to the relative ineffectiveness of drugs against CSCs, which remain viable while retaining their full ability to reproduce the tumor. The development of new strategies is currently hampered by the lack of reliable markers to identify CSCs. One promising surface marker of CSCs in head and neck cancer is the CD44 molecule, which has been shown in preliminary studies to have high specificity, although there are discrepant data because its prognostic value may depend on the specific tumor location. More rigorous studies are needed to investigate the usefulness of CD44 expression in head and neck tumors for possible clinical applicability.

Modified supracricoid laryngectomy: oncological and functional outcomes in the elderly.

BACKGROUND: Supracricoid laryngectomy is an organ preservation surgical technique for early-stage glottic tumors. Modified supracricoid laryngectomy using sternohyoid muscles for neoglottis reconstruction is a new surgical technique. This report evaluates oncological and functional outcomes of this new technique and its feasibility in elderly patients. METHODS: Clinical records from 21 consecutive patients affected by glottic cancer and treated by modified SCL between 2004 and 2009 were retrospectively reviewed. Postoperative parameters and quality of voice after modified SCL were retrospectively reviewed. Actuarial overall survival, disease-specific survival rates, and recurrence-free survival rates were assessed. The functional and oncological outcomes of patients over 65 years were compared with those of patients younger than 65 years of age. RESULTS: There were no postoperative complications and all of the patients had complete swallowing rehabilitation. Twenty of the 21 patients had decannulation. Two patients received total laryngectomy for locoregional relapse. Overall survival and disease-specific survival rates were 100%. Recurrence-free survival rates were 90.1% and 90% in patients younger and older than 65 years of age, respectively. The larynx preservation index was lower in patients who were older than 65 years of age. The postoperative courses with regard to functional outcome and voice quality in elderly patients were similar to those of patients younger than 65 years of age. CONCLUSION: Modified SCL is a new open organ preservation surgical technique that is oncologically safe. The positive functional and oncological outcomes of this surgical procedure allow it to be performed in elderly patients.

Nuclear BMI-1 expression in laryngeal carcinoma correlates with lymph node pathological status.

BACKGROUND: The main cause of treatment failure and death in laryngeal squamous cell carcinoma is metastasis to the regional lymph nodes. The current clinical staging criteria fail to differentiate patients with occult metastasis from patients without metastasis. Identifying molecular markers of the disease might improve our understanding of the molecular mechanisms underlying the pathogenesis and development of laryngeal carcinoma and may help improve clinical staging and treatment. METHODS: Sixty-four previously untreated patients who underwent surgical excision of laryngeal squamous cell carcinoma with neck dissection were included in this study. The expression of B cell-specific Moloney murine leukemia virus integration site 1 (BMI-1) was examined immunohistochemically on formalin-fixed paraffin-embedded primary tissue specimens. RESULTS: Nuclear expression of BMI-1 (nBMI-1) was detected in 32 of the 64 tumors (50%), cytoplasmic expression of BMI-1 (cBMI-1) was detected in 22 (34.4%), and 10 tumors (15.6%) showed no BMI-1 immunoreactivity. High nBMI-1 expression levels (≥ 10) were detected in 28 of the 32 (87.5%) nBMI-1-positive patients. Multivariate analysis including age at diagnosis, grade, tumor location, TNM status, and nBMI-1 expression showed that a high nBMI-1 expression level was an independent prognostic factor for lymph node metastasis. CONCLUSION: The expression of BMI-1 in patients with laryngeal carcinoma seems to correlate with lymph node metastasis.