Electrochemotherapy in the treatment of cutaneous malignancy: Outcomes and subgroup analysis from the cumulative results from the pan-European International Network for Sharing Practice in Electrochemotherapy database for 2482 lesions in 987 patients (2008-2019).

BACKGROUND: Electrochemotherapy (ECT) is a treatment for both primary and secondary cutaneous tumours. The international Network for sharing practices on ECT group investigates treatment outcomes after ECT using a common database with defined parameters. METHODS: Twenty-eight centres across Europe prospectively uploaded data over an 11-year period. Response rates were investigated in relation to primary diagnosis, tumour size, choice of electrode type, route of bleomycin administration, electrical parameters recorded and previous irradiation in the treated field. RESULTS: Nine hundred eighty-seven patients, with 2482 tumour lesions were included in analysis. The overall response (OR) rate was 85% (complete response [CR]: 70%, partial response rate: 15%, stable disease: 11%, and progressive disease: 2%). For different histologies, OR and CR rates for metastases of malignant melanoma were 82% and 64%, basal cell carcinoma were 96% and 85%, breast cancer metastases were 77% and 62%, squamous cell carcinoma were 80% and 63% as well as Kaposi's sarcoma were 98% and 91%, respectively. Variance was demonstrated across histotypes (p < 0.0001) and in accordance with size of lesion treated (dichotomised at diameter of 3 cm (p < 0.0001). Hexagonal electrodes were generally used for larger tumours, but for tumours up to 3 cm, linear array electrodes provided better tumour control than hexagonal electrodes (80%:74%, p < 0.003). For tumours more than 2 cm, intravenous administration was superior to intratumoural (IT) administration (p < 0.05). Current recorded varied across tumour histologies and size but did not influence response rate. In previously irradiated areas, responses were selectively lower for IT administration. CONCLUSIONS: These cumulative data endorse efficiency of ECT across a broad range of histotypes. Analysis of 2482 lesions details subgroup analysis on treatment response informing future treatment choices.

"Tailored" approach to selected recurrent cranio-cervical chordomas: experience and lessons learned.

BACKGROUND: Among chordoma patients, recurrent cases are by far more complex to be managed, and cranio-cervical junction (CCJ) localizations represent a particular challenge due to the complexity of the anatomical region which makes it difficult to obtain a radical resection. METHODOLOGY: We report our personal experience in treating four patients with recurrent CCJ chordoma with "personalized" multiportal and eventually multistage approaches. CONCLUSIONS: Endoscopic endonasal approaches have gained widespread acceptance and are considered the workhorse in most cases of craniocervical junction chordomas. Nonetheless, in some cases of recurrence, or in presence of very lateralized lesions/ anatomical variations midline approaches are either contraindicated or very difficult to perform. In all these cases it seems reasonable to consider a versatile strategy including different approaches, modulating the surgical needs with different answers and solutions offered by the different routes. In other words to personalize as much as possible the approach, being creative and not dogmatic.

Comparison of a purely endoscopic three-layer technique versus pericranial flap for reconstruction of anterior skull base defects after sino-nasal tumor resection: assessment of postoperative frontal lobe sagging and frontal lobe falling.

BACKGROUND: The evolution of endoscopic skull base approaches has enabled surgeons to manage selected skull base tumors through a transnasal endoscope-assisted approach. On the other side, more extensive lesions may require a combined cranioendoscopic approach. In this paper, we analysed and compared the incidence of frontal lobe sagging after endoscopic multilayer (EM) reconstruction versus pericranial flap (PF) reconstruction. METHODOLOGY: Subjects were selected retrospectively according to specific inclusion and exclusion criteria. The degree of frontal lobe sagging after surgery was calculated based on the most inferior position of the frontal lobe relative to the nasion-sellar line defined on preoperative and postoperative imaging. A positive value signified upward displacement, and a negative value represented frontal lobe sagging. RESULTS: Twenty subjects were enrolled in our study. In the EM technique group the average frontal lobe displacement was -2,34 ± 1,55 mm. The average postoperative frontal lobe sagging was -0,45 ± 8,92 mm in subjects reconstructed with the PF. The skull base defect size correlated with the degree of frontal lobe sagging in subjects reconstructed with the PF, but not in the other group and when merging the two groups. CONCLUSIONS: In conclusion, the EM technique and the PF reconstruction showed a good reliability for the closure of anterior skull base defects. Moreover the PF seemed to prevent frontal lobe sagging but, for larger skull base defects, it could be useful to be combined with other autologous or heterologous materials to avoid the frontal lobe falling.

Ecchordosis physaliphora: a cautionary tale.

BACKGROUND: Ecchordosis physaliphora is a congenital, benign lesion originating from notochordal remnants along the craniospinal axis, most frequently located at the level of the clivus and sacrum. Sometimes ecchordosis physaliphora is difficult to recognise and treat, with a total of twenty-six cases described in the literature. METHODS: This study reports on three cases of previously undiagnosed ecchordosis physaliphora presenting with cerebrospinal fluid rhinorrhoea and meningitis. CONCLUSION: Endoscopic transclival or transsphenoid surgery including three-layer (fat, fascia and nasoseptal flap) reconstruction was used in all cases with complete resolution of the symptoms.

Eosinophilic granulomatosis with polyangiitis and laryngeal involvement: review of the literature and a cross-sectional prospective experience.

BACKGROUND: Eosinophilic granulomatosis with polyangiitis and granulomatosis with polyangiitis show variable otorhinolaryngological involvement. Up to 14 per cent of granulomatosis with polyangiitis patients have subglottis involvement; little is known about the laryngeal involvement in eosinophilic granulomatosis with polyangiitis. METHOD: A literature review was conducted, together with a prospective cross-sectional analysis of 43 eosinophilic granulomatosis with polyangiitis patients. All patients underwent fibre-optic laryngoscopy with narrow-band imaging, and completed health-related questionnaires. RESULTS: The literature review showed only two cases of laryngeal involvement in eosinophilic granulomatosis with polyangiitis; in our cohort, no cases of subglottis stenosis were found, but local signs of laryngeal inflammation were present in 72 per cent of cases. Of the patients, 16.2 per cent had a pathological Reflux Finding Score (of 7 or higher). CONCLUSION: Laryngeal inflammation in eosinophilic granulomatosis with polyangiitis is frequent. It is possibly due more to local factors than to eosinophilic granulomatosis with polyangiitis itself. However, ENT evaluation is needed to rule out possible subglottis inflammation. These findings are in line with current literature and worthy of confirmation in larger cohorts.

Nasal cytology: Methodology with application to clinical practice and research.

Nasal cytology is an easy, cheap, non-invasive and point-of-care method to assess nasal inflammation and disease-specific cellular features. By means of nasal cytology, it is possible to distinguish between different inflammatory patterns that are typically associated with specific diseases (ie, allergic and non-allergic rhinitis). Its use is particularly relevant when other clinical information, such as signs, symptoms, time-course and allergic sensitizations, is not enough to recognize which of the different rhinitis phenotypes is involved; for example, it is only by means of nasal cytology that it is possible to distinguish, among the non-allergic rhinitis, those characterized by eosinophilic (NARES), mast cellular (NARMA), mixed eosinophilic-mast cellular (NARESMA) or neutrophilic (NARNE) inflammation. Despite its clinical usefulness, cheapness, non-invasiveness and easiness, nasal cytology is still underused and this is at least partially due to the fact that, as far as now, there is not a consensus or an official recommendation on its methodological issues. We here review the scientific literature about nasal cytology, giving recommendations on how to perform and interpret nasal cytology.

Role of perfusion CT in the evaluation of metastatic nodal tumor response after radiochemotherapy in head and neck cancer: preliminary findings.

OBJECTIVE: To assess changes of CT perfusion parameters (ΔPCTp) of cervical lymph node metastases from head and neck cancer (HNC) before and after radiochemotherapy (RT-CT) and their association with nodal tumor persistence. PATIENTS AND METHODS: Eligibility criteria included HNC (Stage III-IV) candidates for RT-CT. Patients underwent perfusion CT (PCT) at baseline 3 weeks and 3 months after RT-CT. Blood volume (BV), blood flow (BF), mean transit time (MTT) and permeability surface (PS) were calculated. PET/CT examination was also performed at baseline and 3 months after treatment for metabolic assessment. RESULTS: Between July 2012 and May 2016, 27 patients were evaluated. Overall, only 3 patients (11%) experienced tumor persistence in the largest metastatic lymph node. A significant reduction of all PCTp values (p<0.0001), except MTT (from 6.3 to 5.7 s; p=0.089), was observed at 3 weeks post-RT-CT compared to baseline. All PCTp values including MTT were significantly lower at 3-month follow-up compared to baseline (p<0.05). Moreover, a statistically significant association was observed between nodal tumor persistence and high BF values (p=0.045) at 3 months after treatment that did not occur for the other parameters. CONCLUSIONS: Our preliminary findings show that all PCTp except MTT are significantly reduced after RT-CT. High BF values at 3 months post-RT-CT are predictive of nodal tumor persistence.

Non-surgical management of chronic rhinosinusitis with nasal polyps based on clinical-cytological grading: a precision medicine-based approach.

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a common inflammatory disorder that strongly impacts patients' quality of life. CRSwNP is still a challenge for ENT specialists due to its unknown pathogenesis, difficult control and frequent relapse. We tested the hypothesis that a new standardised therapeutic approach based on individual clinical-cytological grading (CCG), may improve control of the disease and prevent the needing for surgery. We analysed 204 patients suffering from bilateral CRSwNP, 145 patients of whom regularly assumed therapy, respecting the planned check-up, and were considered cases; 59 patients were not assuming therapy as indicated and were considered as controls. After five years of standardised treatment, 15 of 145 (10.5%) improved endoscopic staging, 61 of 145 (42%) did not change their endoscopic staging, and 69 of 145 (47.5%) were worse. In the control group, 49 of 59 (83%) were worse by at least two stages (p < 0.05). Patients and controls were stratified basing on clinical and cytological grading as mild, moderate and severe. After patient stratification, in the mild group (n = 27) 92% patients had a constant trend, with no worsening and no need for surgery over a 5-year period, whereas in the mild CCG control group 1 of 59 (1.6%) required surgery (p < 0.05). In moderate GCC (n = 83), 44% of patients did not modify or improve endoscopic staging and 3.6% needed surgery, compared to 13.6% of controls with moderate GCC (p < 0.05). In severe CCG (n = 35), even though no patients achieved significant amelioration of endoscopic grading, 40% of patients were considered as "clinically controlled" and 5.7% of patients underwent surgery, but the percentage was significantly higher (49%) in the control group significant (p = 0.0000). Finally, statistical analyses revealed a clear trend that polyp size increased at a faster rate in the control group than in the treatment group and for each subgroup (low, moderate and severe). The present study suggests a new approach in the management of CRS according to clinical cytological grading that allows defining the grade of CRSwNP severity and to adapt the intensity of treatment. This approach limited the use of systemic corticosteroids to only moderate-severe CRSwNP with a low corticosteroid dosage in comparison with those previously suggested. Our protocol seems to improve the adherence by patients, control of disease and the need for surgery in the long-term.

Adjuvant treatment with a symbiotic in patients with inflammatory non-allergic rhinitis.

Inflammatory non-allergic rhinitis (INAR) is characterized by the presence of an inflammatory infiltrate and a non-IgE-mediated pathogenesis. This retrospective, controlled, multicentre study investigated whether a symbiotic, containing Lactobacillus acidophilus NCFM, Bifidobacterium lactis, and fructo-oligosaccharides (Pollagen®, Allergy Therapeutics, Italy), prescribed as adjunctive therapy to a standard pharmacological treatment, was able to reduce symptom severity, endoscopic features, and nasal cytology in 93 patients (49 males and 44 females, mean age 36.3±7.1 years) with INAR. The patients were treated with nasal corticosteroid, oral antihistamine, and isotonic saline. At randomization, 52 patients were treated also with symbiotic as adjunctive therapy, whereas the remaining 41 patients served as controls. Treatment lasted for 4 weeks. Patients were visited at baseline, after treatment, and after 4-week follow-up. Adjunctive symbiotic treatment significantly reduced the percentages of patients with symptoms and endoscopic signs, and diminished inflammatory cells. In conclusion, the present study demonstrates that a symbiotic was able, as adjuvant treatment, to significantly improve symptoms, endoscopic feature, and cytology in patients with INAR, and its effect may be long lasting.

Chronic skin lichenification as unusual presentation of eosinophilic granulomatosis with polyangitis: case report and literature review.

Eosinophilic granulomatosis with polyangitis (EGPA) is an uncommon ANCA-associated systemic small-vessel necrotizing vasculitis. At times, EGPA presenting manifestations can be very different from the usually recognized disease patterns. We report a 52-year-old female patient with 3 years history of itching. During the time occurred a chronic skin lichenification on her legs and gradually developed a full-blown ANCA-MPO positive EGPA in combination with blood hypereosinophilia, eosinophilic vasculitis at skin biopsy, subclinical asthma and chronic rhinosinusitis.

Standardization procedure for the nasal nitric oxide measurement method using Niox MINO® and the tidal-breathing technique with velum-closure.

Nitric oxide (NO) is a molecule that performs many functions in the human body. The entire respiratory tract can produce NO, but the highest production occurs in the upper respiratory tract, in the paranasal sinuses in particular. The aim of the present study was to assess a new nasal NO (nNO) measurement method using the Niox MINO Nasal® device (Aerocrine AB, Solna, Sweden) and a special procedure, in order to compare the nNO values obtained in 32 healthy subjects with the values found in the international literature. The measured normal nNO values were equal to 426.76±143.27 ppb, with a 95% confidence interval [160.22-733.30]. Males had an average nNO value equal to 446.76±133.63 [178.64 – 714.02], whereas in females the average value was 403.80±154.90 [94.00-713.60]. This study allows us to confirm that we have been able to establish the normal range of nitric oxide quantity produced in the nasal/sinus cavities of healthy individuals using the Niox MINO Nasal® device and tidal-breathing with velum-closure manoeuvre.

How does radiotherapy impact swallowing function in nasopharynx and oropharynx cancer? Short-term results of a prospective study.

The objective of this study is to report the initial results of a prospective trial assessing instrumental deglutition function in nasopharynx and oropharynx cancers after radio or chemoradiotherapy using intensity-modulated radiotherapy (IMRT). IMRT was delivered aiming to spare the swallowing organ at risk (SWOARs) for Stage II-IV naso- and oropharynx cancer. Objective instrumental assessment included videofluoroscopy (VFS), fiberoptic endoscopic evaluation of swallowing (FEES) and oro-pharyngeal-oesophageal scintigraphy (OPES) at baseline and at 1 month after radiotherapy. Dysphagia parameter scores were calculated at each exam after liquid (L) and semi-liquid (SL) bolus intake: pre-deglutition penetration, aspiration, pharyngeal transit time (PTT) and hypopharyngeal retention index (HPRI). Overall, 20 patients (6 nasophaynx and 14 oropharynx) completed treatment and instrumental assessment after 1 month. Comparison between pre- and post-treatment HPRI score values showed a significant worsening in both FEES-L (p = 0.021) and SL (p = 0.02) and at VFS-L (p = 0.008) and SL (p = 0.005). Moreover, a relationship between HPRI worsening at FEES-L and FEES-SL (p = 0.005) as well as at VFS-L and VFS-SL (p < 0.001) was observed. PTT was not significantly affected by radiotherapy (p > 0.2). Only a few patients experienced pre-deglutition penetration (1 patient with base of tongue cancer at FEES-L and SL) and aspiration (1 patient with nasopharynx cancer at OPES-L and FEES-SL) after radiotherapy. Our early results showed that IMRT-SWOARs sparing caused a significant increase in the post-deglutition HPRI score. Longer follow-up will be necessary to evaluate if the increase of HPRI is related to a high risk of developing late aspiration.

Isolated laryngeal leishmaniasis in an immunocompetent patient: a case report.

Isolated laryngeal leishmaniasis in an immunocompetent patient: a case report. OBJECTIVE: Isolated laryngeal Leishmaniasis presents neither explicit laryngeal lesions nor specific symptoms. In fact, it may mimic many inflammatory and neoplastic diseases. Considering the low incidence of this atypical localization, laryngeal Leishmaniasis, is rarely contemplated by physicians in differential diagnoses of laryngeal tumour lesions. We present the case of a 62-year-old immunocompetent subject who developed a single Leishmania mucosal lesion on the left vocal cord, simulating a laryngeal cancer. METHODS: A case report and discussion of the clinical case by referring to the literature. RESULTS: Specific therapy with miltefosine led to clinical and endoscopic improvement. We had no relapse after three years of follow-up. CONCLUSIONS: This clinical case highlights the need to consider isolated laryngeal Leishmaniasis in the differential diagnoses of laryngeal tumour lesions, even in immunocompetent subjects who live in endemic zones, in order to ensure an early and correct therapeutic approach.

Benign tumours affecting the deep lobe of the parotid gland: how to select the optimal surgical approach.

Many types of approaches allow extra-capsular dissection in the deep parotid parenchyma in the treatment of benign tumours. A transcervical approach (TCA), transparotid approach (TPA) and a combined transcervical-transparotid approach (TPTCA) are the three main procedures performed to expose the deep parenchyma. We conducted a retrospective chart review enrolling 24 consecutive patients treated for benign tumours affecting the deep lobe of the parotid. Review of the surgical data was accompanied by careful follow-up to establish surgical morbidity, functional (Frey's Syndrome and first-bite syndrome) and aesthetical outcomes. A TPA was performed in the majority of cases; in 26% superficial parotidectomy was not required (selective deep parotidectomy). Minor's test showed a low rate of Frey's syndrome (3 cases of 23, 13%). No long-lasting first-bite syndrome was reported. Some additional procedures were easily performed in order to improve aesthetical results (rotational flap of sternocleidomastoid muscle, free abdominal fat transfer); these had the same results as selective deep parotidectomy. TCA (or TPTCA) ensures the best control of the facial nerve, providing good exposure and good functional and aesthetical results (without sparing the superficial parenchyma if additional techniques are performed with the aim of reducing skin depression in the treated area). The choice of the approach should have only the aim of safe resection and should not be influenced by aesthetical outcome; the craniocaudal level of the tumour seems to be the best indicator of the feasibility of the procedure also considering the branches of the facial nerve. In our experience, mandibulotomy can always be avoided.

Prophylactic central compartment lymph node dissection in papillary thyroid carcinoma: clinical implications derived from the first prospective randomized controlled single institution study.

BACKGROUND: The benefits of prophylactic central compartment lymph node dissection (pCCND) in papillary thyroid cancer (PTC) are still under investigation. This treatment seems to reduce PTC recurrence/mortality rates but has a higher risk of surgical complications. The lack of prospective randomized trials does not allow definitive recommendations. The aim of this prospective randomized controlled study was to evaluate the clinical advantages and disadvantages of pCCND. PATIENTS: A total of 181 patients with PTC without evidence of preoperative/intraoperative lymph node metastases (cN0) were randomly assigned to either Group A (n = 88) and treated with total thyroidectomy (TTx) or Group B (n = 93) and treated with TTx + pCCND. RESULTS: After 5 years of followup, no difference was observed in the outcome of the two groups. However, a higher percentage of Group A were treated with a higher number of (131)I courses (P = .002), whereas a higher prevalence of permanent hypoparathyroidism was observed in Group B (P = .02). No preoperative predictors of central compartment lymph node metastases (N1a) were identified. Only three patients were upstaged, and the therapeutic strategy changed in only one case. CONCLUSIONS: cN0 patients with PTC treated either with TTx or TTx + pCCND showed a similar outcome. One advantage of TTx + pCCND was a reduced necessity to repeat (131)I treatments, but the disadvantage was a higher prevalence of permanent hypoparathyroidism. Almost 50% of patients with PTC had micrometastatic lymph nodes in the central compartment, but none of the presurgical features analyzed, including BRAF mutation, was able to predict their presence; moreover, to be aware of their presence does not seem to have any effect on the outcome.

The P2X7 receptor-inflammasome complex has a role in modulating the inflammatory response in primary Sjögren's syndrome.

OBJECTIVE: Innate and adaptive immunity may contribute to gland dysfunction in patients with primary Sjögren's syndrome (pSS). The P2X7 receptor (P2X7 R)-NLRP3 inflammasome complex modulates the release of the inflammatory cytokines IL-1ß and IL-18. The presence of P2X7 R in salivary glands suggests an interesting scenario for the initiation and amplification of the innate immune response in pSS. Therefore, the aim of this study was to assess the role of the P2X7 R-NLRP3 inflammasome in pSS. SUBJECTS AND METHODS: Twenty-one consecutive patients with pSS according to the American-European Consensus Group criteria and 15 patients with sicca syndrome (i.e. without Sjögren's syndrome, non-SS) were enrolled in this study, together with six control (CTL) subjects. Expression of the P2X7R-NLRP3 platform and IL-18 was determined by real-time PCR and western blotting in gland specimens and peripheral lymphomonocytes; data were related to patients\x92 clinical, serological and histopathological characteristics. The presence of IL-18 was determined in gland and saliva samples. RESULTS: P2X7 R expression was significantly higher in salivary glands from individuals with pSS than in those from non-SS and CTL subjects. Accordingly, the gene expression levels of the inflammasome components NLRP3, ASC and caspase-1 were significantly higher in pSS gland specimens, and this was paralleled by an increased expression of mature IL-18 in pSS saliva samples. The expression of both the P2X7 R and the inflammasome components was a marker of disease-related glandular involvement, being increased in patients with anti-Ro/SSA positivity and correlated with focus score. CONCLUSION: The results of this study suggest an involvement of the P2X7 R-inflammasome-caspase-1-IL-18 axis in the development of pSS exocrinopathy. This finding provides the basis for studying the complex mechanisms underlying pSS, as well as for developing novel potential therapeutic strategies.

Combined transnasal transcervical robotic dissection of posterior skull base: feasibility in a cadaveric model.

The current surgical trend is to expand the variety of minimally invasive approaches and, in particular, the possible application of robotic surgery in head and neck surgery. For this purpose, we explored the feasibility of a combined transcervical-transnasal approach to the posterior skull base, using the da Vinci Surgical System in 3 cadaver heads. Superb visualization of the sellar, suprasellar and clival regions was possible in all three specimens. The trocars` placement through a transcervical port made a more cephalad visualization possible, eliminating the need to split the palate. The advantages of robotic surgery applied to the posterior cranial fossa are similar to the ones already clinically experienced in other districts (oropharynx, tongue base), in terms of tremor-free, bimanual, precise dissection. The implementation of instruments for bony work will definitely increase the applicability of such a system in the forthcoming years.

Transnasal approach to the medial intraconal space: anatomic study and clinical considerations.

BACKGROUND: The aim of this study was to illustrate the anatomy of the medial compartment of the orbit by comparing the endoscopic transnasal perspective with the external ones. METHODS: 8 orbits from 5 double-injected heads were carefully dissected. An endoscopic anterior transconjunctival dissection was performed in one orbit while an endoscopic transnasal intraconal dissection was conducted in 3 orbits. External dissections (from medial, superior and anterior perspective) were also performed. RESULTS: The role of the medial rectus muscle is emphasised. It represents the first important landmark encountered, covering all the other structures during transnasal approaches. By displacing it, the medial intraconal space with its contents becomes visible: the ophthalmic artery and related branches, the superior ophthalmic vein, the nasociliary nerve and, in the deepest part of the medial compartment, the optic nerve. CONCLUSION: The medial compartment of the orbit can be addressed transnasally. By displacing the medial rectus muscle, it is possible to gain adequate space for the instruments and to control all of the medial compartment, including the medial aspect of the optic nerve.

Extranodal Rosai-Dorfman disease of bone and nose: a case report and review of literature.

Rosai-Dorfman disease (RDD) is a rare benign condition of unknown origin, which was first described in 1969. By histopathology, the disease is composed of sinusoidal lymph node hyperplasia and abundant histiocytes with haemophagocytosis, particularly lymphocytes. It commonly affects lymph nodes, and rarely has an exclusively extra-nodal clinical presentation. Among the so-called "extranodal" sites, the head and neck region, and in particular the nose and paranasal sinuses, are frequently affected. RDD shows a highly variable clinical course that can be partly modified by medical therapy. We present of a case of extra-nodal RDD, with nasal and osseous involvement, which has been followed-up for 19 years. We also discuss its presentation, the most relevant radiographic findings, treatment options and histological findings.