Elective tracheostomy during COVID-19 outbreak: to whom, when, how? Early experience from Venice, Italy.

PURPOSE: The need for prolonged invasive mechanical ventilation in COVID-19 patients is placing the otorhinolaryngologist in front of an increasing request for tracheostomy. Nowadays, there is uncertainty regarding the timing of tracheostomy, the prognosis of these patients and the safety of healthcare workers. The aim of this study is to evaluate the efficacy and safety of tracheostomy placement in patients with COVID-19. METHODS: A retrospective cohort study on 23 COVID 19 patients, to analyse the timing of tracheostomy, the risk factors associated with in-hospital death and the infection of the involved health care workers. Early tracheostomy was defined as ≤ 10 days and late ones > 10 days. RESULTS: The mortality rate of COVID-19 patients admitted to ICU that underwent tracheostomy was 18%. The overall mortality of patients admitted to ICU was 53%. The univariate analysis revealed that early tracheostomy, SOFA score > 6, and D-dimer level > 4 were significantly associated with a greater risk of death. At the multivariate analysis SOFA score > 6 and D-dimer level > 4 resulted as significant factors for a higher risk of death. No health care workers associated with tracheostomy are confirmed to be infected by SARS-CoV2. CONCLUSION: We suggest to wait at least 14 days to perform tracheostomy. In patients with SOFA score > 6 and D dimer > 4, tracheostomy should not be performed or should be postponed. Optimized procedures and enhanced personal protective equipment can make the tracheostomy safe and beneficial in COVID-19 patients.

Multicenter prospective crossover study on new prosthetic opportunities in post-laryngectomy voice rehabilitation.

The aim of this study was to assess the clinical experience of three Italian centers using the third generation Provox Vega prosthesis, in terms of device life and voice outcome, comparing the results with the second generation Provox 2 prosthesis in the same sample. A prospective multicenter crossover study was performed in three phases. In the first phase we performed a reassessment, for enrollment purposes, of patients who were categorized into four different groups [normal ­ group A; radio-treated ­ group B; gastroesophageal reflux disease (GERD) ­ group C; and elderly subjects ­ group D]. In the second and third phases, all patients were monitored for prosthetic device life and assessed for objective and subjective voice characteristics after introducing Provox 2 and Provox Vega prostheses. In patients with Provox 2 prosthesis, the mean life was 165 days in group A, 148 days in group B, 91 days in group C and 188 days in group D. In Provox Vega patients, mean in situ prosthesis life was 213 days in group A, 182 days in group B, 118 days in group C and 227 days in group D. The perceptual voice data showed a better rating across all parameters for the Provox Vega samples compared to those of Provox 2. In this paper, we report the first multicenter crossover study comparing different prosthetic models in the same patients, categorized in relation to different typologies of tracheoesophageal rehabilitative status. Result analyses confirmed an optimal stability of the Provox Vega compared to the Provox 2, in terms of device life and perceptual voice parameters.

Sentinel lymph node biopsy in squamous cell carcinoma of the head and neck: 10 years of experience.

Sentinel node (SN) biopsy of head and neck cancer is still considered investigational, and agreement on the width of the surgical sampling has not yet been reached. From May 1999 to Dec 2009, 209 consecutive patients entered a prospective study: 61.7% had primary tumour of the oral cavity and 23.9% of the oropharynx. SN was not found in 26 patients. Based on these data and definitive histopathological analysis, we proposed six hypothetic scenarios to understand the percentage of neck recurrences following different treatments Among patients with identified SN, 54 cases were pN+: 47 in SN and 7 in a different node. Considering the six hypothetic scenarios: "only SN removal", "SN level dissection", "neck dissection from the tumour site to SN level", "selective neck dissection of three levels (SND)", "dissection from level I to IV" and "comprehensive I-V dissection", neck recurrences could be expected in 6.5%, 3.8%, 2.18%, 2.73%, 1.09% and 1.09% of cases, respectively. SN biopsy can be considered a useful tool to personalize the surgical approach to a N0 carcinoma. The minimum treatment of the neck is probably dissection of the levels between the primary tumour and the level containing the SN(s). Outside the framework of a clinical study, the best treatment can still be considered SND.

Submandibular approach and use of the harmonic instrument in lateral oral cavity and oropharyngeal oncologic surgery.

The approach to the surgical treatment of lateral oral cavity and oro-pharyngeal cancer has undergone many changes over the years, passing from a demolitive approach involving segmental resectioning of the mandible to a conservative approach with temporary mandibulotomy. The complications resulting from these two different approaches invited further review of the various indications related to them. The present report considers, through a retrospective analysis, whether the sub-mandibular approach, which envisages the use of the harmonic instrument, is an oncologically correct alternative and whether it actually reduces the number of early and late complications. From 2003 to 2009, 259 patients underwent surgery for lateral oral cavity and oro-pharyngeal cancer. A sub-mandibular approach was used in 163 patients, and a conservative trans-mandibular approach in 12. The results showed that the number of late complications and T recurrences was significantly lower in those patients in whom the sub-mandibular approach was carried out. There was no difference in the microscopic examination of the resection margins. The use of the harmonic instrument made it possible to perform "en bloc" (T+N) operations working in narrow spaces with less intra-operative bleeding, which contributed to adequate oncological radicality.

Clinical importance of eosinophil count in nasal fluid in patients with allergic and non-allergic rhinitis.

Eosinophil count in nasal fluid (ECNF) was used to differentiate nasal pathologies. Receiver operating characteristic (ROC) curve analysis and the area under the curve (AUC) were performed to evaluate the ECNF's accuracy in distinguishing allergic rhinitis (AR) from non-allergic rhinitis (NAR). We also evaluated the accuracy of ECNF in recognizing patients with mild and severe symptoms of rhinitis and patients with ineffective and effective clinical responses to antihistamines. 1,170 consecutive adult patients with a clinical history of rhinitis were studied. ECNF's median in AR was 6.0 and 2.0 in NAR and the best cut-off value was > 3.0, AUC = 0.75. ECNF's median in AR with mild nasal symptoms was 3.0 and 7.0 with severe symptoms, and the best cut-off value was 4.0, AUC = 0.90. ECNF's median in NAR with mild nasal symptoms was 2.0 and 8.5 with severe symptoms, and the best cut-off value was > 4.0, AUC = 0.86. ECNF's median in AR with effective clinical response to antihistamines was 4.0 and 8.0 with ineffective response, the best cut-off value was < or = 5.0, AUC = 0.94. ECNF's median in NAR with an effective clinical response to antihistamines was 1.0 and 2.0 with ineffective response, and the best cut-off value was < or = 3.0, AUC = 0.64. Our results suggest an interesting practical use of ECNF data as evaluator of the clinical severity both AR and NAR. As predictor of the clinical response to antihistamines, ECNF is accurate only in patients with AR. The ECNF's performance was moderately accurate in distinguish patients with AR and NAR.

An extended use of the sentinel node in head and neck squamous cell carcinoma: results of a prospective study of 100 patients.

Most studies concerning the use of the sentinel node technique in head and neck cancers have included clinically N0 patients with primary early stage tumours of the oral cavity or upper part of oropharynx; furthermore, node sampling has been performed during the same session, but separately from the tumour. The perspective of avoiding unnecessary neck dissection, without increasing the risk of delayed diagnosis of lymph node metastasis, is rewarding, not only for early stage tumours of the oral cavity but also for tumours in advanced stages and/or at different anatomic sites. In the attempt to establish the reliability of extended use of the sentinel node technique, 100 consecutive untreated patients (from 1999 to 2002) with tumours located in the oral cavity, oropharynx, hypopharynx and larynx, at any T stage, entered the study. N+ patients with paramedian tumours and contralateral clinically negative nodes were also enrolled. After injection of the 99mTc albumin microcolloid, pre- and intra-operative evaluations with a gamma-probe were done. N0 patients (59) were submitted to mono- or bilateral selective neck dissection; the N+ patients (41) received homolateral dissection of all levels and contralateral selective dissection. An en bloc resection of the tumour was performed both in N0 and N+ patients. In the N0 group, histological examination showed no evidence of metastases in "hot" nodes in 34 patients and also the remaining nodes were negative. Metastases were found in one or more of the gamma-probe positive nodes (14 cases), or in a closely located node at the same level (2 cases) or in a node close to a "hot" area of the submandibular salivary gland (1 case). In 8 patients, lymphoscintigraphy did not identify any sentinel node and histology of all lymph nodes was negative for metastases. In the N+ group, no metastases were found in the sentinel nodes of 21 patients and also the remaining nodes were negative; in 4 patients, metastases were found in sentinel nodes. In 16 patients, lymphoscintigraphy did not identify any sentinel node and histology of all lymph nodes was negative for metastases. In no patients were metastases found outside the level containing the lymph node identified as sentinel by the gamma-probe. In conclusion, the strategy of the sentinel node is reliable, but, to be confirmed as a standard approach, it requires trials with a larger number of patients. The technique requires a multidisciplinary and well "amalgamated" team. It may likely be used also in T3 and T4 oro-hypopharyngeal and laryngeal primary tumours and to determine surgical treatment of the contralateral neck in patients with N2a, N2b, N3 on T close to the midline.

Nasopharyngeal cancer WHO type II-III: monoinstitutional retrospective analysis with standard and accelerated hyperfractionated radiation therapy.

The aim of this study is to assess the impact of prognostic factors in patients with locoregionally advanced nasopharyngeal cancer (NPC), WHO type II-III, treated with two different radiation therapy (RT) schedules: standard radiation therapy (SRT), and accelerated hyperfractionated radiation therapy (HART), with or without sequential chemotherapy. Between January 1986 and December 1999, 78 consecutive NPC patients were treated either with SRT (until August 1993) or with HART (from September 1993). Of the 78 patients, 60 were males and 18 females, the median age was 56 years (range 14-83). Nine patients had a non-keratinizing carcinoma (WHO type II) and 69 an undifferentiated carcinoma (WHO type III). Five-year overall survival rate (OS) was 62%. Two months after RT, 73 patients were in complete remission. Disease-free survival (DFS) rates at 5 years were: 85% for the HART and 59% for the SRT group, respectively. A multivariate analysis, age (hazard ratio, HR=4.17 for > or = 60 vs. <50 years) and N-stage (HR=3.56 for N3a-N3b vs. N0-N1) were significant for survival, whereas N-stage (HR=8.23 for N3a-N3b vs. N0-N1) and RT schedule (HR=0.30 for HART vs. SRT) were significant for DFS. In our experience, HART achieved higher DFS rates than SRT; however, HART did not favourably affect OS. Toxicity was comparable in the two RT schedules.

Squamous cell carcinoma of the hypopharynx treated with surgery and radiotherapy.

A series of squamous cell carcinomas (SCC) of the hypopharynx treated with combined surgery and radiotherapy is presented to highlight the results of treatment at an early stage of disease. A retrospective mono-institutional analysis was performed on 153 previously untreated patients with SCC of the hypopharynx, seen between 1980 and 1995 at our institution. Univariate and multivariate analyses were performed using the Cox proportional hazard model. The overall five-year specific, and non-specific, disease survival rates were 68 per cent (95 per cent confidence interval, CI: 60-77) and 47 per cent (95 per cent CI: 39-56), respectively. Compared with other series, this study is characterized by treatment at an earlier stage, better prognosis, and a higher number of multiple malignancies. Twenty-two per cent of hypopharyngeal SCCs were diagnosed during the staging procedures for a different head and neck SCC and 14 per cent during the follow-up for a previous tumour. Multivariate survival analysis of clinical and pathological factors confirmed the clinical class of tumour (T) and node (N) and the nodal capsular rupture as prognosticators of disease.

Prognostic significance of pleural lavage cytology after resection for non-small cell lung cancer.

OBJECTIVE: In the staging of lung cancer, pleural effusion that is malignant on cytologic examination is regarded as T4 disease, and curative resection cannot be performed. We conducted this study to determine whether cancer cells can be present in the pleural cavity with no pleural effusion, to investigate the factors contributing to that occurrence, and to evaluate its prognostic significance. METHODS: Eighty-five patients (77 males, eight females) with a median age 60.1-+/--7.9 years (31--74 years) underwent a major lung resection, due to lung cancer in our department. From January 1998 to December 1999, 30 pneumonectomies, seven bilobectomies, 46 lobectomies and two wedge-resections were performed. Chest wall resection was performed in four patients. After performing a posterolateral thoracotomy and lung resection with extended mediastinal lymph node dissection, the pleural cavity was filled with 1 l physiologic saline solution (PSS) and the fluid was shaken. The lavage fluid was suctioned off (S1). Immediately after the lavage, the pleural cavity was refilled with 3 l PSS. The surgeon washed out the pleural cavity by hand for 1 min and the fluid was suctioned off. Finally, the pleural cavity was refilled with 1 l PSS and a new lavage fluid was suctioned off (S2). A cytologic examination was carried out for each sample. RESULTS: The pathology report showed 39 adenocarcinomas, 33 squamous-cell, two adenosquamous, four large-cell, two neuroendocrine and five undifferentiated carcinomas. S1 was positive in eight patients (9.4%), while S2 was positive in four patients (4.7%). The correlation of positive pleural lavage and infiltrated lymph nodes demonstrated a statistically significant relation between presence of N2 disease and positive S2 sample (P = 0.049). No significant correlation existed between positive lavage sample (S1 or S2) and TNM stage, level of T, extent of tumor invasion, kind of operation, histological type or differentiation of the cancer (Chi square test). The mean follow-up is 11.3 +/- 6.2 months (4--22 months). There are 78 patients alive. A significance difference in survival was identified in-patients with positive S1 (P = 0.0081), and positive S2 (P = 0.0251) (Kaplan--Meier). CONCLUSION: The cytologic results of lavage were positive for malignant cells in eight of 85 patients (9.4%). The existence of cancer cells in the pleural cavity can be the result of their exfoliation or surgical manipulations. The mechanical irrigation subdivides the percentage of positive samples. Our study supports that the positive findings on pleural lavage cytology is an essential prognostic factor.

Immunological changes in peripheral blood and in lymphoid tissue after treatment of HIV-infected subjects with highly active anti-retroviral therapy (HAART) or HAART + IL-2.

This study presents the immunophenotypic and functional analysis of lymphocyte subsets obtained from peripheral blood and lymphoid tissue from HIV+ individuals treated with highly active anti-retroviral therapy (HAART) alone or in combination with 6 million units international (MUI) s.c. IL-2. Before treatment, the HIV+ patients had reduced CD4 and increased CD8 values in the peripheral blood and lymphoid tissue and impaired cytokine production by peripheral blood mononuclear cells (PBMC). After 24 weeks of treatment, all the HIV+ patients demonstrated increased CD4 values in peripheral blood and lymphoid tissue. The use of IL-2 did not promote an additional CD4 expansion compared with HAART alone; increased 'naive' and CD26+ CD4 cells and reduced CD8 cells were found in the peripheral blood and lymphoid tissue of the IL-2-treated, but not of the HAART-treated patients. Both types of treatment induced a significant reduction of the CD8/CD38+ cells. While HAART alone had negligible effects on cytokine production by PBMC, the combined use of HAART + IL-2 was unable to increase the endogenous production of IL-2, but caused an increase of IL-4, IL-13 and interferon-gamma (IFN-gamma) and a reduction of monocyte chemoattractant protein-1 (MCP-1) production. These data suggest that, although in this schedule IL-2 has minimal efficacy on CD4 recovery when compared with HAART alone, it produces an increase of 'naive' and CD26+ CD4 cells and a partial restoration of cytokine production. These data may be used to better define clinical trials aiming to improve the IL-2-dependent immunological reconstitution of HIV-infected subjects.

Radiation treatment of glottic squamous cell carcinoma, stage I and II: analysis of factors affecting prognosis.

PURPOSE: At least in some European Countries, there is still considerable controversy regarding the choice between surgery and radiotherapy for the treatment of patients with early laryngeal-glottic carcinoma. METHODS AND MATERIALS: Two hundred and forty-six patients with laryngeal-glottic neoplasms, Stage I-II, were treated with radical radiotherapy. Before radiotherapy the patients were evaluated to determine the surgical procedure of choice. Either 66-68.4 Gy (33-38 fractions) or 63-65 Gy (28-29 fractions) of radiation therapy (RT) were administered. The overall disease free survival was determined for each subgroup of patients. Univariate and multivariate analyses were performed to determine significant prognostic variables. RESULTS: Five- and 10-year overall survival rates were 83 and 72%, respectively. At a median follow-up of 6 years 204 patients are alive and disease free. No patient developed distant metastases. One patient died of a large local recurrence, 38 patients died of causes unrelated to their tumor, and 3 patients were lost to follow-up. The multivariate analysis confirmed that performance status (PS), macroscopic presentation of the lesion, and persistence of dysphonia after radiotherapy are significant prognostic factors. CONCLUSIONS: According to the multivariate analysis, the patients with PS > 80 and with exophytic lesions are eligible for radical RT. The surgical procedure proposed for each patient was not found to be an independent prognostic factor.

Squamous cell carcinoma of the posterior pharyngeal wall: characteristics compared with the lateral wall.

Squamous cell carcinoma of the posterior oro- and hypopharyngeal wall (SCCPPW) is a relatively rare tumour. A retrospective investigation of 63 patients with SCCPPW and 449 patients with carcinoma of the lateral oro- and hypopharyngeal wall, treated between 1964 and 1992, has been carried out. Most SCCPPW were asymptomatic, macroscopically superficial and at early stages. They were usually detected by chance during an examination for a different type of malignancy. Fifty-seven percent of SCCPPW patients had multiple tumours; however this occurrence did not alter the survival rate. The crude five-year survival rate for SCCPPW was 22 percent and was not significantly different from that of patients with lateral wall tumours. Moreover, both local control and recurrences also were not statistically different.

Glyburide-sensitive K+ channels in cultured rat hippocampal neurons: activation by cromakalim and energy-depleting conditions.

Previous studies in our laboratory have shown that cromakalim activates a tetraethylammonium-sensitive K+ current in cultured embryonic rat hippocampal neurons. This phenomenon was further characterized using whole-cell voltage-clamp and single-channel recording techniques. Glyburide (1-25 microM), an antagonist of ATP-sensitive K+ channels, produced a concentration-dependent depression of the cromakalim-activated current. In contrast, charybdotoxin (100 nM), an antagonist of some Ca(2+)-dependent and other K+ channels, not only failed to block the effect of cromakalim but actually produced a moderate enhancement of the cromakalim-activated K+ current. Neither glyburide nor charybdotoxin affected resting or voltage-activated K+ currents in the absence of cromakalim. Exposure of the cells to energy-depleting conditions (0.24 micrograms/ml oligomycin and 10 mM 2-deoxy-D-glucose) also activated an outward current. Single-channel recordings in the cell-attached configuration showed that cromakalim (100 microM) stimulated the opening of flickery single channels having a unitary conductance of approximately 26 pS and a prolonged burst duration (mean open time, approximately 131 msec); similar channel openings were observed in patches from cells exposed to energy-depleting conditions. In patches containing a single K+ channel, the open probability in the presence of cromakalim was approximately 0.6 and in the presence of energy-depleting conditions was approximately 0.8; in the absence of either of these treatments, channel openings were not observed. Glyburide produced a reversible inhibition of the channels activated by cromakalim and energy-depleting conditions. These data provide additional support for the existence of ATP-sensitive K+ channels in central neurons and indicate that the K+ channels whose opening is stimulated by cromakalim are likely to be of the ATP-sensitive type.

BRL 34915 (cromakalim) enhances voltage-dependent K+ current in cultured rat hippocampal neurons.

The whole cell voltage-clamp recording technique was used to study the effects of the benzopyran antihypertensive agent BRL 34915 on voltage-dependent outward currents in cultured rat hippocampal neurons. Extracellular perfusion with BRL 34915 (10-500 microM) produced a dose-dependent increase in the sustained (minimally inactivating) voltage-dependent outward current without altering the transient outward current (IA) or producing a change in the resting current at -60 mV. One-half maximal facilitation of the sustained outward current occurred at 40 microM and maximal facilitation (59%) at 100 microM. The increase in outward current occurred at all potentials where hippocampal neurons exhibited outward rectification (greater than -30 mV). The effect of BRL 34915 was slow to develop (requiring as long as 5-15 min to achieve maximal effect) and persisted for at least 10-15 min after cessation of the drug superfusion. Like the sustained outward current recorded under control conditions, the outward current augmented by BRL 34915 was inhibited by the K+ channel blocker tetraethylammonium (20 mM). These results indicate that BRL 34915 can enhance the activity of sustained voltage-dependent K+ channels in mammalian CNS neurons.