Temporal evolution of quality of life in patients endoscopically treated for sinonasal malignant tumors.

BACKGROUND: The aim of our study is to assess which factors may affect the quality of life (QoL) and its fluctuation over time in adult patients who received endonasal endoscopic oncologic sinus surgery (EOSS) for sinonasal malignancies (SNM) in our center. METHODOLOGY: We analyzed EOSS cases for primary SNM from January 2015 to June 2020. For each patient, we have recorded the age at treatment, gender, smoking habits, use of psychotropic drugs for mood disorders, stage, histotype, type of surgical resection, need for skull-base reconstruction, development of postoperative major complications, and the use of adjuvant intensity-modulated radiotherapy (IMRT). We evaluated the patient's performance status pre-treatment using the ECOG scale. Quality of life was measured using three questionnaires (SNOT-22; ASK-9; EORTC QLQ-C30 version 3). RESULTS: Fifty-five patients were enrolled in our study, of whom thirty-two (58.18%) received adjuvant IMRT. Overall, a significant improvement in all QoL outcomes was observed at eighteen months, while, female sex, higher ECOG scores, advanced stage of disease, and adjuvant IMRT were associated with worse QoL. After 18 months the delta in QoL between women and men worsened (in SNOT-22 and EORTC QLQ-GLOBAL) while if only the most fragile patients according to ECOG are considered, this difference was reduced for both tools. CONCLUSION: Our analysis revealed that IMRT is the element that has the greatest impact on patient's quality of life, in association with the female sex, ECOG >2, and advanced stage of the disease.

The role of Narrow Band Imaging (NBI) in the diagnosis of sinonasal diseases.

BACKGROUND: Narrow band imaging (NBI) endoscopy is an optical method that helps to characterise tissue vasculature. Its appli- cation in sinonasal pathology remains scarce and a systematic study of its application to rhinology is lacking. The aim of this study is to analyse and describe the normal sinonasal mucosa under NBI light and to characterise the microvascular features of various sinonasal pathologies. We also want to suggest a classification of the patterns, peculiar to this district, and to evaluate whether they can be indicative of a specific physiological or pathological condition. METHODS: Digital videos and images under white light and NBI of 103 patients (82 evaluated) with 29 sinonasal pathologies and 55 controls (33 evaluated). were independently analysed by three otolaryngologists and the final pattern was then arranged for each image, reaching an agreement between the individual evaluations. RESULTS: Once the appearance of normal sinonasal (SN) mucosa was established (SN1), four patterns for the pathological mucosa were described and a working classification was proposed (SN2, SN3, SN4, SN5). We calculated specificity (80.6% vs 90.6%), sensi- tivity (20% vs 38.5%), PPV (46.1% vs 50%), NPV (54.7% vs 85.7%) and accuracy (53% vs 80.3%) of the ability of SN4 and SN5 pattern to discriminate between benign and malignant nasal neoformations. CONCLUSIONS: This is the first study to propose a systematic NBI description and a classification of the vasculature of healthy and pathological mucosa in the sinonasal tract. Our preliminary results show that this technique can help in the workup of several rhinologic conditions and especially in distinguishing benign from malignant tumors.

Mesenchymal stem cells are enriched in head neck squamous cell carcinoma, correlates with tumour size and inhibit T-cell proliferation.

BACKGROUND: Cancer is a multifactorial disease not only restricted to transformed epithelium, but also involving cells of the immune system and cells of mesenchymal origin, particularly mesenchymal stem cells (MSCs). Mesenchymal stem cells contribute to blood- and lymph- neoangiogenesis, generate myofibroblasts, with pro-invasive activity and may suppress anti-tumour immunity. METHODS: In this paper, we evaluated the presence and features of MSCs isolated from human head neck squamous cell carcinoma (HNSCC). RESULTS: Fresh specimens of HNSCC showed higher proportions of CD90+ cells compared with normal tissue; these cells co-expressed CD29, CD105, and CD73, but not CD31, CD45, CD133, and human epithelial antigen similarly to bone marrow-derived MSCs (BM-MSCs). Adherent stromal cells isolated from tumour shared also differentiation potential with BM-MSCs, thus we named them as tumour-MSCs. Interestingly, tumour-MSCs showed a clear immunosuppressive activity on in vitro stimulated T lymphocytes, mainly mediated by indoelamine 2,3 dioxygenase activity, like BM-MSCs. To evaluate their possible role in tumour growth in vivo, we correlated tumour-MSC proportions with neoplasm size. Tumour-MSCs frequency directly correlated with tumour volume and inversely with the frequency of tumour-infiltrating leukocytes. CONCLUSIONS: These data support the concept that tumour-MSCs may favour tumour growth not only through their effect on stromal development, but also by inhibiting the anti-tumour immune response.

Potential use of acupuncture in the treatment of first bite syndrome.

OBJECTIVES: First bite syndrome (FBS) is an early postoperative pain syndrome characterized by the sudden onset of pain in the parotid region at the first bite of each meal. The etiology is not certain, hence a standardized therapy does not exist. METHODS: A 50-year old woman referred to us complaining of a swelling in the right parotid region. Fine-needle aspiration biopsy (FNAB) was diagnostic for pleomorphus adenoma of the deep lobe of the parotid gland. A 50-year old man presented with a mass in the right side of the neck, FNAB was diagnostic for parapharyngeal space neurinoma. The first patient was submitted to total parotidectomy with facial nerve preservation, the second to extracapsular dissection of the tumor. A week after surgery both patients developed FBS. A qualitative/quantitative description of pain was obtained by means of a self-coded questionnaire. The score ranges from 8 to 44, corresponding to the lowest and the highest discomfort possible, respectively. Acupuncture was used to treat these 2 patients. The treatment protocol comprised 6 sessions, one per week, lasting 30 minutes each. RESULTS: Our questionnaire was administered before and after treatment and the score dropped from 33 to 25 in the female, from 30 to 15 in the male patient. CONCLUSION: FBS is a complication of upper cervical surgery with a high morbidity rate. We describe the first two cases of FBS that were successfully treated with acupuncture in our ENT department. We believe that this procedure may represent a valid therapeutic alternative in the future.

Detection of putative stem cell markers, CD44/CD133, in primary and lymph node metastases in head and neck squamous cell carcinomas. A preliminary immunohistochemical and in vitro study.

OBJECTIVES: Investigators hypothesized that cancer stem cells (CSCs) could play a role in determining cancer progression by metastasizing to cervical lymph node (N+) and then influencing prognosis of head and neck squamous cell carcinomas (HNSCCs) patients. DESIGN: To identify CSCs in HNSCCs and their clonogenic capacity. SETTING: In vitro study. PARTICIPANTS: Putative CSCs from 29 primary HNSCCs and 19 corresponding node metastases were analyzed. MAIN OUTCOME MEASURES: Immunohistochemical (IHC) was performed, and CSCs' clonogenic in vitro capacity was tested; ones epithelial nature of cancer cells forming colonies was confirmed by a second IHC, fluorescence-activated cell sorting (FACS) analysis helped in counting CD44/CD133-CSCs markers percentage expression in HNSCC tumour-derived cultures. RESULTS: Immunohistochemical showed CD44 (93.1%) and CD133 (10.34%) expression; FACS-analysis showed the enrichment of CD44/CD133 cancer cells, with the highest clonogenic capacity of CD44+-subpopulation; a higher CD44 rates were documented from N+ subcultures than from original tumours (P < 0.05). CONCLUSIONS: A putative cancer stem-like cell population is detectable in HNSCCs, and our findings show their in vitro clonogenic capacity by demonstrating that CD44+-cultured cells are the main population proliferating obtained by N+ HNSCC metastases, emphasizing their possible role in tumour progression.

Dissection with harmonic scalpel versus cold instruments in parotid surgery.

BACKGROUND: The harmonic scalpel (HS) has been used successfully in several head and neck surgical procedures. Some authors highlighted its advantages in reducing operative time, blood loss, and damages to surrounding tissue. In our study, we compared the results obtained during parotidectomy using the HS with the traditional approach to determine the benefits of the HS. METHODS: 130 patients with benign parotid tumors were enrolled and randomized into two groups for this prospective study. 63 patients underwent HS parotidectomy, and 67 patients received a parotidectomy using cold instruments and bipolar electrocautery hemostatic control (CI). 20 HS and 2 CI patients did not meet the inclusion criteria requirements, and were excluded. RESULTS: The admission time was significantly shorter in the HS group than the CI group (3.9 ± 1.2 days and 4.7 ± 1.4 days, respectively, p < 0.01). In the early post-operative period, 84% of HS patients and 60% of CI cases showed no facial nerve impairment (p = 0.01). Significantly more CI patients than HS patients showed the onset of Frey's syndrome (29% and 9%, respectively, p = 0.01). Multivariate stepwise regression analysis confirmed the reduction in admission length (Odds Ratio (OR): 0.62; p = 0.02) and the lower risk of Frey's syndrome (OR: 0.29; p = 0.04) in HS compared to CI parotidectomies. CONCLUSIONS: In parotid surgery, the HS is useful in preventing Frey's syndrome and reducing early transitory facial nerve dysfunction and admission times, and results in decreased medical costs and increased quality of life.

Salvage surgery after unsuccessful radiotherapy in early glottic cancer.

Surgery is the main therapeutic option to control recurrent laryngeal cancer after radiotherapy (RT) relapse. Most RT-recurred cancer is treated aggressively; although, conservative laryngeal surgery was attempted in selected cases. Here, we report our experiences with salvage laryngeal surgery for early glottic cancers that did not respond to RT. We analyzed files from 1980 to 2006 and selected 173 patients surgically treated for a RT-failed early glottic carcinoma (stage I-II according to 2010 TNM: 114 T1N0, 59 T2N0). Among them, 47 patients (27%) underwent a salvage partial laryngectomy (SPL) and 126 (73%) had a salvage total laryngectomy (STL). When compared with initial T staging, we found 61% of lesions were up-staged, 31% had the same staged lesion, and only 8% were down-staged (according to rTNM). No statistically significant differences were found in terms of disease-free survival and overall survival when SPL and STL patients were compared. Univariate analysis showed that T, rT, and rTNM were prognostic factors for overall survival (p = 0.045, p = 0.028, and p = 0.037, respectively); yet, these significances were lost in multivariate analysis. Our results suggest that salvage surgery is feasible in most cases of RT-recurred early glottic cancer; although, a conservative approach achieves good oncological and functional results only in select RT-recurred patients.

Prognostic role of internal jugular vein preservation in neck dissection for head and neck cancer.

BACKGROUND AND OBJECTIVES: Sparing internal jugular vein (IJV) in neck dissection for head and neck cancer is controversial. We aimed at evaluating the prognostic impact of IJV preservation. METHODS: We examined 206 files of head and neck cancer patients who underwent radical or modified radical neck dissection at the Otolaryngology University of Florence. The site of primary tumor was larynx and hypopharynx in 44.66%, oropharynx in 25.24%, oral cavity in 23.3%, unknown in 4.85%, salivary glands and rhinopharynx in 0.97%. In 60.19% the IJV was resected, in 39.81% preserved. Prognostic impact of IJV preservation was assessed by Kaplan-Meier and multivariate analysis. RESULTS: Neck recurrence occurred in 25.2%: the IJV was resected in 42.31%, in 57.69% preserved (P = 0.02). At multivariate analysis, neck recurrence resulted significantly associated to extracapsular spread (ECS) (P = 0.009), IJV preservation (P = 0.01), positive margins (P = 0.02). In ECS positive patients, a higher risk of neck recurrence was documented for IJV preservation (P = 0.012). A worse prognosis was observed for patients with IJV spared (P = 0.06). CONCLUSIONS: IJV preservation is associated with an increased risk of neck failure and a worse outcome, mainly in patients with ECS of nodes.

New surgical technique for endoscopic management of anterior glottic web.

OBJECTIVES: In this study we report a new endoscopic technique for the management of anterior glottic web (AGW). Previously, various procedures with endoscopic or open surgical approaches have been described for the treatment of symptomatic AGW. We present an original, highly effective endoscopic technique that seems to have several advantages over traditional approaches. METHODS: We used this novel technique in a preliminary series of four patients. Using a CO2 laser, a curvilinear mucosal flap based on the web is elevated from the superior surface of one vocal chord. The web is divided, and the flap is sutured at the inferior surface of the opposite vocal chord, ensuring that no raw surfaces will be left exposed on this side of the larynx. We accurately describe the technique, displaying diagrams of the surgical steps. RESULTS: In three cases, a restoration of the laryngeal airway, with complete resolution of the AGW, was achieved. A limited residual web persisted close to the anterior commissure in the fourth patient. CONCLUSIONS: The new endoscopic technique utilized in our preliminary series of patients is a simple, repeatable, and effective surgical procedure for managing AGW.

Surgical management of surgery and radiation induced peristomal neck ulcerations.

UNLABELLED: PROBLEMS/OBJECTIVE: Non-healing cervical skin ulcerations with concomitant necrosis of the subcutaneous tissue and muscle is a rare but feared complication of radiotherapy that can arise in cervical regions. Constant erosion of the surrounding tissue by the expansion of the necrotic front can threaten important structures. Very few reports in the literature deal with the surgical management of these injuries. METHODOLOGY: This paper reports on two cases of non-healing, slow-growing cervical ulcerations that occurred as a result of radiotherapy and surgery. RESULTS: After unsuccessful conservative treatment, definitive surgical repair was performed to achieve reparation of the defect and protect deep structures. The onset and characteristics of the ulcerations as well as the reconstructive options are discussed. CONCLUSIONS: In the treatment of surgery and radiotherapy induced chronic cervical wounds, non surgical medical treatment should be always attempted for at least 6 months, and should always include hyperbaric oxygen therapy. If conservative methods fail, surgical repair by means of transposition of well vascularized tissue is mandatory to prevent serious complications such as major vessel rupture or fistulas.

How to avoid life-threatening complications following head and neck space infections: an algorithm-based approach to apply during times of emergency. When and why to hospitalise a neck infection patient.

BACKGROUND: Head and neck space infections present with a potential mortality rate of 40-50 per cent. This paper proposes an algorithm-based management of head and neck space infection to prevent life-threatening events. METHODS: A total of 225 patients with head and neck space infection were prospectively analysed at our institution. An experimental scoring system determined the level of clinical risk for the development of major complications. Accordingly, patients were classified into three risk groups: low-, intermediate- and high-risk. RESULTS: Only intermediate- and high-risk patients were hospitalised. Intermediate-risk patients received intravenous medical therapy with daily re-evaluation; 18 of them required delayed surgery. Of the high-risk patients, three required immediate surgical treatment and five received delayed surgery, while in five cases medical therapy was the only treatment received. Low-risk patients were treated in an out-patient setting. CONCLUSION: The algorithm-based management of head and neck space infection was successful in enabling the avoidance of lethal complications onset.

Role of nitric oxide in angiogenesis and tumor progression in head and neck cancer.

BACKGROUND: Angiogenesis (formation of new blood vessels) is associated with tumor growth and metastasis in patients with solid tumors, including those of the head and neck. Nitric oxide (NO) production may contribute to these processes. We assessed the role of the NO pathway in angiogenesis and tumor progression in patients with head and neck cancer. METHODS: Biochemical assays were used to measure NO synthase (NOS) activity and cyclic guanosine monophosphate (cGMP) levels in specimens of tumor and normal mucosa obtained from 27 patients. Microvessels in tumor specimens were identified by CD-31-specific immunohistochemical staining. Associations between microvessel densities, levels of NOS, and cGMP were examined by use of two-sided statistical tests. Tumor specimens and human squamous carcinoma A-431 cells were grown as explants on the corneas of rabbits, and the effect of the NOS inhibitor N(omega)-nitro-L-arginine-methyl ester (L-NAME) was tested. RESULTS: Levels of total NOS, inducible NOS, and cGMP were higher in tumor specimens than in specimens of normal mucosa (all P<.0001). Tumor specimens from patients with lymph node metastases presented a higher total NOS activity (P = .005) and were markedly more vascularized than tumor specimens from patients with no lymph node involvement (P = .0002). Microvessel density at the tumor edge was an independent predictor of metastasis for this series of patients (odds ratio = 1.19; 95% confidence interval = 1.07-2.89; P = .04). A-431 cells and tumor specimens exhibiting high levels of NOS activity induced angiogenesis in the rabbit cornea assay; when NO production was blocked, tumor angiogenesis and growth were repressed. CONCLUSIONS: The NO pathway appears to play a key role in tumor angiogenesis and spread in patients with head and neck cancer.

Evolution of elective neck dissection in N0 laryngeal cancer.

Management of cervical lymph node metastasis is one of the most challenging problems facing clinicians dealing with head and neck cancer. A retrospective evaluation has been made of results in N0 laryngeal cancer patients treated from 1978 to date by comparing historical data reported in related papers previously published by our institution. The medical records of 2207 consecutive patients with cN0 SCC of the larynx were used as the source of data in the present study. Together with primary treatment, 759 (34.4%) received at least unilateral elective neck dissection, while the remaining 1448 (65.6%) were admitted to a wait-and-see protocol. Overall, in the electively dissected patients (ED): 128 (16.9%) cases were submitted to classical radical neck dissection, while 403 (53.1%) cases were submitted to functional neck dissection (FND) and 228 (30.0%) cases to jugular node dissection (JND, removing Level II, III and IV). In 125 of the ED group, a neck procedure on the contralateral N0 neck was associated, of which 15 were RNDs, 35 FNDs and 75 JNDs, respectively. Based on this large series population, the change in the philosophy was evaluated concerning elective neck treatment in N0 laryngeal cancer, from RND through FND towards JND. As far as concerns the reliability as a staging procedure, no statistically significant difference was found between RND, FND and JND (p = 0.794). The 5-year neck recurrence rate, as estimated by the Kaplan Meier, method, for all ED patients, was 7.7%. No significant difference in the rate of 5-year neck recurrence was detected between RND, FND and JND groups (p = 0.178). In the survival curves, no differences, in terms of actuarial survival by Kaplan Meier analysis, were observed, in our series, as far as concerns type of elective neck dissection performed (p = 0.222). In conclusion, following a critical revision of 25 years' experience, at our Institution, in the management of cN0 necks in laryngeal cancer patients, definitive changes were observed in the surgical approach to the treatment of occult disease in cN0 cases. JND, compared to more extensive neck dissections, did not show statistically significant differences in terms of neck control (p = 0.233), in terms of impact on survival (p = 0.122) and in terms of accuracy as staging procedure (p = 0.794).

Microsatellite analyses of recurrence or second primary tumor in head and neck cancer.

BACKGROUND: In head and neck squamous cell carcinoma, distinguishing second primary tumours and recurrences may help to orient clinical decisions concerning therapy. PATIENTS AND METHODS: A panel of eight microsatellite markers was used to analyse the loss of heterozygosity and genomic instability in a selected group of 32 patients experiencing a recurrence after having undergone surgery for oral or oropharyngeal carcinoma, in order to establish the clonality and origin of the recurrence. RESULTS: Twenty-three patients showed genetic changes in primary and/or relapsing tumour DNA: clonally-related patterns were detected in six cases, whereas the different patterns between paired tumours indicated the presence of a second primary tumour in 17 cases. None of the markers was informative in nine cases. CONCLUSION: Our observations suggest that only a small proportion of patients have primary and secondary tumours developing from a single contiguous altered field (thus indicating a common clonal origin), whereas the metachronous tumour arises in unrelated fields in the majority of cases.

Prediction of occult neck metastases in laryngeal carcinoma: role of proliferating cell nuclear antigen, MIB-1, and E-cadherin immunohistochemical determination.

The aim of this study is to investigate the predictive value of proliferative activity assessment and E-cadherin expression by means of immunohistochemistry in identifying patients with laryngeal squamous cell carcinoma at a high risk for occult node metastasis. Thirty consecutive patients treated for laryngeal carcinoma with false clinically negative nodes (occult metastases, pN+) between the years 1980 and 1990 were selected for this study. A group of 30 cases with negative cervical lymph nodes (pN-) having a similar anatomic site and tumor size distribution was used as control. In each case, several histological parameters, including grade, pattern of invasion, number of mitosis (x10 high-power field), tumor inflammatory infiltrate, and tumor sclerosis, were assessed. Proliferative activity was determined using immunohistochemical staining for proliferating cell nuclear antigen (PCNA) and MIB-1. Other putative prognostic factors investigated at the immunohistochemical level were the cell adhesion molecule E-cadherin and two oncoproteins, p53 and c-erbB-2. In pN+ cases, the expression of PCNA and MIB-1 was significantly higher than in the pN- group. Moreover, a significant loss of E-cadherin expression was observed in carcinomas with occult metastases. No differences in p53 and c-erbB-2 oncoproteins were found between pN+ and pN- cases. Among the other pathological parameters examined, only histological grade was significantly associated with the presence of occult metastases, but on multivariate analysis, this relationship was lost. We conclude that PCNA, MIB-1, and E-cadherin are independent predictors of occult nodal disease in laryngeal squamous cell carcinoma, and their immunohistochemical determination could be useful in identifying patients with clinically negative lymph nodes who are at considerable risk for occult metastases and who may benefit from elective neck dissection.

bcl-2 protein expression correlates with recurrence and survival in early stage head and neck cancer treated by radiotherapy.

Inherent cellular radioresistance plays a critical role in the failure of radiation therapy (RT). The proto-oncogene bcl-2 encodes a protein that inhibits apoptosis, a common mechanism of cell death induced by several genotoxic agents, including gamma-radiation. Thus, it is likely that bcl-2 gene expression could be involved in the complex mechanisms of radioresistance in human tumors with some prognostic implications. In this study, we analyzed the predictive relevance of bcl-2 expression on 5-year disease-free and overall survival in patients with early stage squamous cell carcinoma of the head and neck (SCCHN) primary treated with RT. The expression of bcl-2 was analyzed by immunohistochemistry on paraffin-embedded sections from 71 consecutive stage I-II SCCHN patients treated with curative RT. We detected bcl-2 protein in 21% of SCCHN studied. A suggestive association was observed between tobacco exposure and bcl-2 protein expression (P < 0.1); this association was stronger in those patients who failed primary RT (P = 0.03). Moreover, we documented a higher rate of bcl-2 immunoreactive tumors in postirradiated biopsies from relapsed patients than in preirradiated ones (P = 0.03). In both univariate and multivariate analyses, bcl-2 expression was the most important indicator for disease-free survival (P = 0.08 and P = 0.01, respectively) and overall survival (P = 0.004 and P = 0.05) within 5 years of RT. The present study indicates that the proto-oncogene bcl-2 is abnormally expressed in some SCCHN, and its expression may prove to be a useful tool in selecting patients for conventional RT with clear prognostic implications.

Loss of p53 gene mutation after irradiation is associated with increased aggressiveness in recurring head and neck cancer.

The p53 gene plays a pivotal role in the control of a checkpoint during G1 and in the apoptotic program. It has been postulated that alterations of p53 may influence radio-sensitivity and prognosis in several malignancies. We studied the p53 gene status of 35 consecutive head and neck cancer patients who failed primary radiotherapy (RT) in preirradiated and postirradiated tumor samples using DNA single-strand conformational polymorphism analysis. Sixteen of 35 (46%) preirradiated samples presented with band shifts suggestive of point mutations in one or two exons. Eleven of these tumors (69%) showed the same shift even in the postirradiated samples. Exons 5 and 8 were prevalently affected in this group. Five tumors (31%) lost the mutation following RT. The missed mutations clustered in exon 7. All mutations were confirmed by sequencing. Actuarial analysis demonstrated increased survival in patients with tumors bearing a p53 gene mutation in both preirradiated and postirradiated samples (P = 0.05 and P = 0.01, respectively). We also found that loss of p53 gene mutation in postirradiated cancers is associated with a significantly shorter disease-free interval (P < 0.02) and a worse prognosis (P < 0.05). A possible explanation in such cases is clonal selection by RT of more aggressive and radioresistant cell subpopulations, which are wild-type for the p53 gene. Taken together, our data suggest that not only p53 gene status but also the pattern of mutations could modulate the response of tumor cell to RT in vivo.

Pharyngocutaneous fistula following total laryngectomy: analysis of risk factors, prognosis and treatment modalities.

The aim of this study was to establish the incidence, risk factors, and the management of pharyngocutaneous fistula (PCF) after primary and salvage total laryngectomy. A retrospective, match-paired analysis of 86 patients who developed fistula after total laryngectomy was carried out and compared with a control group of 86 patients without fistula, randomly selected from a pool of 352 total laryngectomies, performed between January 1999 to October 2014. The overall incidence of PCF in the series was 24.4%; we recorded rates of 19.0%, 28.6% and 30.3% following primary total laryngectomy (PTL), salvage laryngectomy post-radiotherapy (RT-STL) and salvage laryngectomy postchemoradiotherapy (CRT-STL), respectively. Multivariate analysis revealed that the relative risk of fistula was respectively 2.47, 3.09 and 7.69 for hypoalbuminaemia ≤3.5 g/dL, RT-STL and CRT-STL. An early onset of PCF within 10 postoperative days was recorded in case of salvage total laryngectomy. The management of PCF significantly differed between PTL, RT-STL and CTRT-STL, with exclusive conservative treatment for PTL (93.55%), while in the CRT-STL group surgical closure with regional flaps (58.82%) prevailed. Conservative management, adjuvant hyperbaric oxygen therapy and surgical closure were equally distributed in the RT-STL group. Thorough knowledge of patient-related risk factors and its prognostic value, allows the surgeon to better evaluate preventive strategies with the aim of minimising fistula formation, hospitalisation times and related costs.