Hyper-late major response after 5†years of nivolumab: role of treatment beyond progression in head and neck cancer.

Patients with recurrent/metastatic (R/M) platinum-refractory squamous cell carcinoma of the head and neck (SCCHN) have fewer treatment options and harbor an especially poor prognosis. Maintaining treatment with anti-PD1 agents beyond response evaluation criteria in solid tumors-defined disease progression (TBP) has been shown to be efficacious in several solid tumors, including head and neck cancer. We present the case of a platinum-refractory locally recurrent, PD-L1-negative hypopharyngeal carcinoma, that received second-line nivolumab which was then maintained beyond progression under the following criteria: no Eastern Cooperative Oncology Group performance status deterioration, no rapidly progressive disease, no severe toxicity, and evidence of overall treatment benefit. The patient achieved a partial response 8 months after starting second-line nivolumab, with progressive disease at 26 months, then followed by the first TBP with nivolumab lasting for 15 months due to a new tumor progression. A second TBP with nivolumab lasting for 7 months, was followed by a third TBP with nivolumab for 12 months and achieving a major tumor response. Treatment is still ongoing 60 months after starting nivolumab, with excellent tolerance to therapy. Maintaining anti-PD1 agents beyond progression is an efficacious treatment option for patients with R/M SCCHN, that may achieve very durable disease control and even late major responses.

Durable complete remission with local therapies after neoadjuvant and adjuvant nivolumab in recurrent/metastatic head and neck cancer.

Up to 10-15% of patients with first-line recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) present with platinum-refractory disease. The anti-PD1 nivolumab is the first therapeutic option in this setting achieving a 19.2% objective response rate and a 7.7-month median overall survival (OS). Given the poor prognosis of platinum-refractory patients, those showing slow progressive disease with no functional status deterioration should maintain nivolumab beyond progression in the absence of severe or unmanageable toxicities. Another strategy is to use local therapies such as radiotherapy and surgical tumor resection in cases of oligometastatic or oligoprogressive disease. Both strategies may significantly improve disease control and OS in these populations. We present the case of a patient with platinum-refractory disease treated with first-line nivolumab beyond progression who achieved a durable complete response after palliative radiation and surgical resection of five tumor lesions. To our knowledge, this is the first reported case of an R/M HNSCC treated with such a strategy outside a clinical trial and contributes to the evidence for combining anti-PD1 agents and local therapies in selected patients with R/M HNSCC.

Safety and preliminary activity of pembrolizumab-carboplatin-paclitaxel in heavily pretreated and/or fragile patients with PDL1-positive recurrent/metastatic head and neck cancer.

Novel chemo-immunotherapy (chemo-IO) combinations should be evaluated, which may be suitable for cisplatin-unfit or fluoropyrimide-ineligible patients with recurrent or metastatic squamous cell carcinoma of head and neck (R/M SCCHN) to guarantee higher and deeper responses than IO alone. The aim of the present study was to review our experience using pembrolizumab-carboplatin-paclitaxel (pembro + CP) in patients with R/M SCCHN. This was a retrospective study of patients with R/M SCCHN who received pembro + CP in any-line via a compassionate-use program. The present study evaluated safety using Common Terminology Criteria for Adverse Events v4.0, compliance, overall response rate (ORR) and disease control rate (DCR) using Response Evaluation Criteria in Solid Tumors 1.1, duration of treatment, progression-free survival (PFS) and overall survival (OS). Between March 2020 and August 2021, 10 patients were identified (median age, 64 years; female, 60%; Eastern Cooperative Oncology Group 2, 80%). A total of 8 patients received pembro + 3-weekly carboplatin-paclitaxel (3wkCP). A total of 2 patients received pembro + weekly carboplatin-paclitaxel (wkCP). Patients received a median of 3 lines (range, 0-6) of systemic therapy prior to pembro + CP and 80% received IO in previous lines. Grade 1-2 adverse events (AEs) occurred in 100% of patients. Grade 3-5 AEs occurred in 30% of patients [all grade 3 (anemia, neutropenia, thrombopenia, hypertension)]. The mean numbers of pembro + wkCP and pembro + 3wkCP cycles were 2.5 and 6. The ORR (n=7) was 14% (1/7) with one complete response. The DCR was 43% (3/7). The median PFS (n=7) and OS (n=10) times since pembro + CP were 5 months (95% CI, 1-9) and 6 months (95% CI, 0.5-14), respectively. In this small retrospective series of heavily pretreated patients, pembro + CP was well tolerated, and compliance was high. Studies should be conducted to prospectively evaluate the safety and efficacy of this combination in patients with R/M SCCHN.

Fetal development and growth of the fissula ante fenestram in the human ear.

Since the fissula ante fenestram (FAF) is considered as a focus of otosclerotic lesion and a route of perilymph leakage, there are few description of prenatal development of the cartilaginous canal passing though the cochlear wall. We examined the sagittal and frontal histological sections of the ear from 32 human fetuses at 8-37 weeks of gestational age. At 8-12 weeks, in the immediately anterior side of a connection between the cochlear and canalicular parts of the otic capsule cartilage, the FAF appeared as a tear of a cartilage between the basal and second turns of the cochlea. The tear became a slit opening to the scala vestibuli. At 13-15 weeks, the FAF, less than 1.2 mm in length, had the anterosuperior and postero-inferior apertures: the former was near the geniculate ganglion and became closed after 15 weeks, while the latter approached the oval window. Third trimester fetuses, the FAF, 1.5-2.0 mm in length, consistently carried a single, postero-inferior aperture extending along the anterior margin of the oval window and it contained no definite epithelium and vessel. Although it was endochondral ossification, there was no clear zonation in cartilage cells of the FAF. A mechanical stress during three-dimensional coiling of the cochlear ducts seemed to provide the FAF. After the FAF was established, the stapes footplate might use a part of the inferior aperture for the syndesmosis. A specific ossification was seen in the FAF, but it might rarely cause the pathological syndesmosis.

Analysis of aerosol production and aerosol dispersion during otologic surgery.

BACKGROUND: As a respiratory disease, the transmission of Coronavirus disease (COVID-19) is mainly caused by small droplets and aerosols. Healthcare personnel are particularly exposed during otologic surgery given the continuity with the nasopharynx, where the viral load is high, and the use of high-speed instruments. The purpose of the present study is to test a model of droplet dispersion produced in the performance of a drilling procedure on human bone to provide information about its distribution and size of the deposit in similar conditions to those of an operating theatre, to design different preventive measures. MATERIAL AND METHOD: A mastoidectomy and trans-labyrinthine approach were performed on an embalmed human corpse using for irrigation during drilling methylene blue dye in physiological saline solution (pss) at a concentration of 0.324 mg/mL. The distribution of the drops was stablished using semi-absorbent papers of size 52 cm × 42 cm covering the area around the dissection field to a radius of 150 cm and on the corpse at different heights to check vertical dispersion. The collected deposit material was analysed with the microscope at different magnification objectives. RESULTS: Droplets between 2 µm and 2.6 cm were obtained. The visualization of the coloured droplets in the horizontal plane at a magnification of 1.5 was detected at 150 cm from the focus of emission of milling particles. DISCUSSION: According to our study, bone drilling with high speed motors under continuous saline irrigation in a haemorrhagic surgical field increases the amount of aerosols exposing healthcare personnel to additional airbone particles. This risk does not end in the operating rooms as particles smaller than 2 µm can be suspended in the air for hours and could exit the operating theatre due to the use of positive pressure systems. Thus, the use of N95, FFP2, FFP3 or PAPRS should be considered and the development of hood systems to prevent the dispersion of aerosols during these procedures should be considered.

Toxocariasis affecting brain stem and skull base.

BACKGROUND: Toxocariasis is a helminthic infection caused by a nematode that mainly affects populations in tropical and subtropical latitudes. Humans are potential paratenic hosts, and clinical disease occurs as a result of parasite migration through intestinal tissue. We present a clinical case of otorhinolaryngological affectation by Toxocara canis. CASE PRESENTATION: A 60-year-old male from Ecuador, resident in Spain for 5 years, evaluated in the emergency department for presenting headache, otorrhea and left ear pain. Computed tomography (CT) and magnetic resonance imaging (MRI) reported a large mass of the nasopharynx with infiltration of the skull base, intracranial extension and a lesion in the left pons without being able to exclude metastases. Two Functional Endoscopic Sinus Surgery (FESS) biopsies were negative for malignancy. Despite not meeting the diagnostic criteria established by the existing literature, the clinical and radiological presentation, the presence of risk factors, a positive serology for Toxocara canis (IgGELISA) and the absence of alternative diagnosis were considered sufficient criteria to establish toxocariasis with inflammatory lesions in the nasopharynx and pons as the most probable diagnosis. Treatment with albendazole (400 mg / 12 h) and corticosteroids (1 mg / kg for 5 days) was started and continued for one month. Post treatment negative serology, and MRI and CT post treatment controls were performed after one year, both showing a decrease in lesion of the clivus as well as the pons. CONCLUSIONS: With the appropriate personal history, toxocariasis should be included in the differential diagnosis of infiltrating lesions of the skull base with a negative study of tumor histology. Albendazole treatment has been shown to control and cure the disease.

Cartilage invasion patterns in laryngeal cancer.

The cartilaginous invasion determines the T and is one of the most common sources of mistake in tumor staging. Also it is of great importance when planning any therapeutic alternative. In the latest revision of the TNM classification a clear distinction is made between infiltration of cartilage without going through it, considered a T3 recently and that would be a T4 according to the previous classification, and those going through the cartilage, classified as T4a. While this classification makes the difference in depth of infiltration, it does not emphasize the extent of invasion. This paper provides a detailed description of the laryngeal cartilage tumor infiltration by whole organ serial section in which the invasion is considered both horizontal (transcartilaginous) and vertical (extent of invasion) and establishing patterns of three-dimensional infiltration of the cartilage. This is a cross-sectional study of prevalence. 275 records of patients treated for laryngeal squamous cell carcinoma between 1995 and 2000 were reviewed. The pathological processing of laryngectomy surgical specimens was performed following the method of whole organ serial section described by G. F. Tucker. The following patterns of cartilaginous infiltration were defined: (1) transcartilaginous infiltration; (2a) partial focal infiltration of the cartilage: infiltration not going through the cartilage but occupying one third or less of its extent; (2b) partial extensive infiltration of the cartilage: infiltration occupying two thirds or more of its length and (3) no cartilage infiltration: tumor in contact with the cartilage (paraglottic space) but without affecting it. 161 patients met the inclusion criteria. The most frequent tumor location was supraglottic (58 cases) followed by glottic (47). 109 patients (67.7 %) were treated with total laryngectomy. Partial surgical techniques were performed in the remaining cases. TNM tumor staging was performed according to the results of pathological study (pTNM). 72.06 % (116) were classified as advanced laryngeal tumors (pT3 and pT4). 46 % of patients showed some extent of laryngeal cartilage infiltration (thyroid, cricoid, arytenoids, epiglottis). The cartilage most frequently infiltrated was the thyroid in 48 patients (29.8 %) and when it is affected, in most cases (66.7 %), the infiltration is transcartilaginous. The next most common pattern is partial focal infiltration (27 %). In the cricoid cartilage, the most common pattern of infiltration is focal partial infiltration (52.6 %). Of the 19 cases with infiltration of the cricoid, there are 12 cases with extra laryngeal invasion through a cricothyroid membrane perforation. The study of laryngeal cancer by laryngeal whole serial section has been proved to be very useful in offering a high precision pTNM staging and a detailed description of the infiltration of cartilage. We have seen that when the thyroid cartilage is infiltrated the tumor often passes through the cartilage. However, there are cases where the tumor is extremely aggressive, being very widespread in cartilage thickness without actually crossing it. The isolated infiltration of the cricoid cartilage is exceptional.

Pharyngo-cutaneous fistula: an old problem revisited.

CONCLUSION: Pharyngo-cutaneous fistula is the most common complication after total laryngectomy (TL), with many factors linked to its emergence. However, it has rarely been associated with the type of pharyngeal suture. We conclude that the technique of surgical closure of the pharynx and care in the tightness of the suture seem to be fundamental factors for pharyngo-cutaneous fistula development. OBJECTIVE: The aim of present work was to determine whether the type of pharyngeal suture can be considered as a major risk factor for developing a pharyngo-cutaneous fistula following TL. METHODS: We carried out a series of 157 consecutive TLs. In the first 90 procedures, we performed a pharyngeal closure technique with T-shaped interrupted stitches reinforced with constrictors. In the other 67 cases, a doubled continuous suture technique with reinforcement with the cutaneous flap was developed. RESULTS: In all, 25.5% of the cases sutured with the interrupted stitches developed a fistula while only 2.9% of the patients that underwent continuous suture developed a fistula.