Retrograde cricopharyngeal dysfunction and treatment with botulinum toxin: a systematic review.

PURPOSE: Retrograde cricopharyngeal dysfunction (RCPD) is a disease first described systematically in 2019. The main symptom is inability to belch due to cricopharyngeal muscle dysfunction. Other symptoms include gurgling noises, chest pain, bloating, and excessive flatulence. This paper aims to describe RCPD, the aetiology and diagnosis, treatment options, follow-up, and treatment with botulinum toxin (BT). METHODS: A systematic review was done according to the PRISMA guidelines, using the databases PubMed, Embase, and Cochrane at 8/3/2024. The search combined BT with different descriptions of RCPD. All papers were screened by two authors. RESULTS: 120 papers were identified in the search. After screening 13 papers describing 472 patients in total were included. Mean age was 29.3 years with 51.1% men. Diagnosis was established in 82.4% of the cases by symptomatology, 2.1% by high-resolution manometry, and 15.3% by oesophagoscopy. The mean amount of BT was 66 units (U). Mean follow-up time was 13 months. After 1-4 weeks 93.7% had an effect post-treatment and 81.0% after 6 months. Common symptoms were inability to belch (99.8%), chest pain and/or bloating (95.4%), gurgling noises (84.9%), and excessive flatulence (75.9%). Common complications were mild and transient dysphagia (59.4%) and reflux (35.4%). CONCLUSION: The accumulated numbers of patients with RCPD indicates a growing attention to the plausible condition. Injection with BT is a good and safe treatment of RCPD. Most patients only experience mild and transient complications to the treatment. Much is still unknown about RCPD and conditions for setting the diagnosis needs to be evaluated and established internationally.

Comparison of Transoral and Transcervical Ultrasonography with MRI for the Diagnostic Work-Up of Oropharynx Tumors: A Protocol for a Multicenter Clinical Trial (SPOTUS).

This study protocol for a prospective, multicenter, diagnostic, clinical trial describes the integration of transoral and transcervical ultrasonography (US) in the initial clinical work-up of patients referred to tertiary head and neck cancer centers with suspected oropharyngeal cancer. The study evaluates the blinded detection rate of oropharyngeal tumors and their US-estimated size and T-stage before histopathology and cross-sectional imaging are available. Magnetic resonance imaging (MRI) scans will be prospectively rated while blinded to T-site histopathology and US. The primary outcome measures of diagnostic accuracy, including sensitivity, specificity, positive and negative predictive values, and overall accuracy, will be reported for both US and MRI. A sub-analysis of prospectively rated 18F-Fluorodeoxyglucose (FDG) positron emission tomography/computerized tomography (PET/CT) scans in patients with clinically suspected unknown primary tumors will also be compared to US and MRI. Secondary outcome measures, including a comparison of tumor size estimation between US, MRI, and CT, will also be reported. This prospective multicenter study will provide clinically impactful information regarding the use of transoral and transcervical US for the diagnostic work-up of oropharyngeal cancer.

Characterization of patients with odontogenic necrotizing soft tissue infections in the head and neck area. A retrospective analysis.

OBJECTIVE: Necrotizing soft-tissue infection (NSTI) in the head and neck area may develop from odontogenic infections. The aim of this study was to characterize patients with NSTI in the head and neck with odontogenic origin in a well-defined prospectively collected cohort. MATERIAL AND METHODS: Patients with NSTI in the head and neck, hospitalized between 2013 and 2017 at Copenhagen University Hospital and registered in the Scandinavian INFECT database were included. Medical records of identified patients and from the INFECT database were screened for a defined set of data including the primary focus of infection, comorbidities, predisposing factors, clinical and radiographic diagnostics, course of treatment, and treatment outcome. RESULTS: Thirty-five patients with NSTI in the head and neck area were included in the study. A total of 54% had odontogenic origin, primarily from mandibular molars, and 94% had radiographic signs of infectious oral conditions. Overall, comorbidities were reported in 51% with cardiovascular disease being the most prevalent. In 20%, no comorbidities or predisposing conditions could be identified. The overall 30-day mortality rate was 9%. CONCLUSIONS: More than half of NSTI cases in the head and neck region had an odontogenic origin, and special attention should be paid to infections related to mandibular molars.

Electrochemotherapy in Mucosal Cancer of the Head and Neck: A Systematic Review.

Electrochemotherapy (ECT) is a local ablative treatment that is based on the reversible electroporation and intracellular accumulation of hydrophilic drug molecules, which greatly increases their cytotoxicity. In mucosal head and neck cancer (HNC), experience with ECT is limited due to the poor accessibility of tumors. In order to review the experience with ECT in mucosal HNC, we undertook a systematic review of the literature. In 22 articles, published between 1998 and 2020, 16 studies with 164 patients were described. Curative and palliative intent treatment were given to 36 (22%) and 128 patients (78%), respectively. The majority of tumors were squamous cell carcinomas (79.3%) and located in the oral cavity (62.8%). In the curative intent group, complete response after one ECT treatment was achieved in 80.5% of the patients, and in the palliative intent group, the objective (complete and partial) response rate was 73.1% (31.2% and 41.9%). No serious adverse events were reported during or soon after ECT and late effects were rare (19 events in 17 patients). The quality-of-life assessments did not show a significant deterioration at 12 months post-ECT. Provided these preliminary data are confirmed in randomized controlled trials, ECT may be an interesting treatment option in selected patients with HNC not amenable to standard local treatment.

Calcium electroporation for recurrent head and neck cancer: A clinical phase I study.

BACKGROUND: Calcium electroporation is a novel cancer treatment, which combines temporary cell permeability from electroporation with a high influx of calcium intracellularly resulting in cancer cell necrosis. METHODS: A phase I trial performing calcium electroporation on 6 patients suffering from recurrent head and neck cancer. In general anesthesia, intratumoral calcium injections were followed by electroporation. Safety was monitored by adverse events registration, serum Ca2+, ECG, and pain scores. Tumor response was measured on PET/MRI scans. RESULTS: Procedures were performed without complications. No serious adverse events, signs of hypercalcemia, or cardiac arrhythmias were observed. Two months post-treatment tumor responses on MRI: three partial responses, one stable disease, and two progression. Responses on PET: one partial metabolic disease, four with stable metabolic disease, and one not evaluable. One patient was without clinical evidence of disease after 12 months of observation. CONCLUSION: Calcium electroporation is feasible and safe in head and neck tumors. Clinical responses were observed in three of six patients, warranting further studies. LEVEL OF EVIDENCE: Level 4.

An update on head and neck cancer: new entities and their histopathology, molecular background, treatment, and outcome.

The head and neck region harbor numerous specialized tissues of all lineages giving rise to a plethora of different malignancies. In recent years, new types and subtypes of cancer has been described here due to the recognition of their histological and molecular characteristics. Some have been formally accepted in the most recent classifications from the World Health Organization (WHO) and American Joint Committee on Cancer (AJCC) as distinct diseases due to characteristics in clinical presentation, outcome, and treatment. In particular, this applies to malignancies of the salivary gland, sinonasal tract, and oropharynx. In this overview, we present the most recent developments in the classification, histopathological characteristics, and molecular features of head and neck cancer. The clinical and radiological characteristics, outcome, and treatment options including perspectives for targeted therapies, are discussed.

The DAHANCA 32 study: Electrochemotherapy for recurrent mucosal head and neck cancer.

BACKGROUND: Electrochemotherapy is an established treatment for cutaneous tumors. This study aimed at determining efficacy of electrochemotherapy in recurrent head and neck cancer. METHODS: Phase II clinical trial in patients with recurrent head and neck carcinomas with no curative treatment options. Electrochemotherapy was performed under general anesthesia. Primary endpoint was tumor response (CT scanning) evaluated at week 8. Secondary endpoints included biopsy results, MRI and fluorodeoxyglucose-positron emission tomography scanning, safety, toxicity, pain score, and quality-of-life questionnaires. RESULTS: Of 26 patients treated, 5 (19%) achieved complete response, 10 (39%) partial response, resulting in an objective response of 58%. Two responders remain without recurrence. No serious adverse events occurred during treatment. Four events occurred posttreatment: one bleeding episode, two episodes with mucosal swelling, and one patient died due to disease progression. CONCLUSION: Electrochemotherapy is efficient against local recurrence of head and neck cancer with an overall response rate of 58%.

Endoscopic electrochemotherapy for esophageal cancer: a phase I clinical study.

BACKGROUND AND STUDY AIMS: Esophageal cancer is on the rise in the western world and the disease has a poor 5-year survival prognosis below 20 %. Electrochemotherapy is a treatment where a chemotherapeutic drug is combined with locally applied electrical pulses, in order to increase the drug's cytotoxicity in malignant cells. This study presents the first results with electrochemotherapy treatment in esophageal cancer. PATIENTS AND METHODS: In this first-in-human trial, six patients with advanced esophageal cancer were treated with electrochemotherapy using intravenous bleomycin. All side effects and adverse events (AEs) were registered and the patients were later evaluated with gastroscopy and 18F-fluorodeoxyglucose positron emission tomography/magnetic resonance imaging (18F-FDG PET/MRI). RESULTS: Treatment were well tolerated, main AEs being nausea, vomiting, oral thrush, pneumonia, retrosternal pain, fever, and hoarseness. No serious complications were observed. Five patients had a visual tumor response confirmed by gastroscopy. In two cases, these findings were confirmed with 18F-FDG PET/MRI as it revealed a reduction of total tumor mass. CONCLUSION: Electrochemotherapy in patients with advanced esophageal cancer was conducted without major safety concerns. This study paves the way for larger studies, which may further elucidate response rates for and side effects of this new treatment.

European Research on Electrochemotherapy in Head and Neck Cancer (EURECA) project: Results from the treatment of mucosal cancers.

AIM: Electrochemotherapy is an effective local treatment for cutaneous tumours and metastases. In this prospective trial, six European institutions investigated electrochemotherapy in recurrent, mucosal head and neck tumours. PATIENT AND METHODS: Forty-three patients with recurrent mucosal head and neck tumours and no further curative or reasonably effective palliative treatment options were enrolled and treated with electrochemotherapy. Patients were treated in general anaesthesia using intravenous or local injection of bleomycin followed by delivery of electric pulses to the tumour area. Primary end-point was local tumour response. Secondary end-points were safety and toxicity, overall and progression free survival, and quality-of-life. RESULTS: Thirty-seven patients were evaluable for tumour response, pain score, side-effects and quality of life questionnaires. Six patients were not evaluable due to lost follow-up, disease progression or death before evaluation. Intention to treat analysis revealed an objective response of 56% (complete response 8 (19%), partial response 16 (37%), stable disease 10 (23%), progressive disease 3 (7%), and not evaluable 6 (14%)). Three patients (7%) remained in complete response at 30, 34, and 84 months post-treatment. The treatment procedure was generally well tolerated. Swelling of the mucosa was observed in the first days after treatment. Pain and use of pain medication rose temporarily; fatigue and dysphagia were also noted in the quality of life assessment. CONCLUSION: Electrochemotherapy can be applied to mucosal head and neck recurrent tumours accessible to the procedure with promising objective response, survival and toxicity profile. Attention should be paid to post-treatment swelling and planning of pain medication. These favourable results indicate that electrochemotherapy could play a role in patients with recurrent head and neck cancer.

Cross-Cultural Translation, Adaptation and Reliability of the Danish M. D. Andeson Dysphagia Inventory (MDADI) in Patients with Head and Neck Cancer.

The objectives were to translate and culturally adapt the M.D. Anderson Dysphagia Inventory (MDADI) into Danish and subsequently test the reliability of the Danish version. The MDADI was translated into Danish and cross culturally adapted through cognitive interviews. The final version was test-retest evaluated in a group of head and neck cancer (HNC) patients who responded to the questionnaire twice with a mean of eight days apart. Interclass correlation coefficient, Cronbach's alpha, floor and ceiling effects, standard error of measurement and minimal detectable change were investigated. Fourteen patients were interviewed on the comprehensibility of the Danish MDADI, and all found the questionnaire meaningful, easy to understand, non-offensive and to include relevant aspects of dysphagia related to HNC. Sixty-four patients were included in the test-retest study. Especially, one item in the emotional scale (E7) appeared to be often misinterpreted, and ceiling effects were found in all four subdomains (global, emotional, functional and physical). The four subdomains and the composite score showed acceptable test-retest reliability and internal consistency in a Danish population of HNC patients. The Danish MDADI is reliable in terms of internal consistency and test-retest reproducibility and can be used in assessing the health-related quality of life in head and neck cancer patients with dysphagia.

Electrochemotherapy of mucosal head and neck tumors: a systematic review.

BACKGROUND: Electrochemotherapy, the combination of electroporation and chemotherapy, is mainly used in the palliative setting for treatment of cutaneous and subcutaneous metastases; however, new applications are continuously being explored. Patients with head and neck cancer are primarily treated with surgery and/or radio-chemotherapy. In the setting of local recurrence with no further curative treatment options available, electrochemotherapy could be of value. We therefore performed a systematic search of the present literature. MATERIALS AND METHODS: Eligible studies presented data from patients with head and neck cancer treated across the mucosal surface with electrochemotherapy. The search resulted in 11 studies with a total of 72 patients. RESULTS: Overall complete response was reported as good, especially in primary small tumors. Side effects were minor in primary tumors whereas large, recurrent tumors displayed more frequent side effects and some serious adverse events. Design and structure of the studies differed considerably, making general comparisons difficult. CONCLUSION: Few studies concerning electrochemotherapy on mucosal head and neck tumors are available and they are not easily comparable. Overall response to treatment is good; nonetheless, further systematic studies are warranted.

European Research on Electrochemotherapy in Head and Neck Cancer (EURECA) project: Results of the treatment of skin cancer.

Electrochemotherapy is an effective and safe method for local treatment of cutaneous and subcutaneous tumours, where electric pulses cause increased permeability of cell membranes in the tumour mass, enabling dramatically enhanced effectiveness of bleomycin and other hydrophilic drugs. Here, we report results of a European multi-institutional prospective study of the effectiveness of electrochemotherapy in the treatment of skin cancer of the head and neck (HN) area, where standard treatments had either failed or were not deemed suitable or declined by the patient. A total of 105 patients affected by primary or recurrent skin cancer of the HN area were enrolled; of these, 99 were eligible for evaluation of tumour response. By far, the majority (82%) were treated only once, and 18% of patients had a second treatment. The objective response was highest for basal cell carcinoma (97%) and for other histologies was 74%. Small, primary, and treatment-naive carcinomas responded significantly better (p < 0.05), as investigated by univariate analysis. Electrochemotherapy was well tolerated and led to a significant improvement of quality of life, estimated by the European Organisation for Research and Treatment of Cancer quality of life questionnaires. At 1-year follow-up, the percentages of overall and disease-free survival were 76% and 89%, respectively. Electrochemotherapy is an effective option for skin cancers of the HN area and can be considered a feasible alternative to standard treatments when such an alternative is appropriate. The precise role for electrochemotherapy in the treatment algorithm for non-melanoma skin cancer of the HN region requires data from future randomised controlled studies. (ISRCTN registry N. 30427).

Clinically isolated laryngeal sarcoidosis.

Laryngeal sarcoidosis is rare (0.5% of patients with sarcoidosis), the pathogenesis is unknown and the optimal treatment remains a matter of debate. We undertook this study to elucidate possible pathogenic factors in clinically isolated laryngeal sarcoidosis and to describe results of supraglottoplastic surgery. From 1995 to 2009, we identified six patients with histologically proven sarcoidosis of the larynx treated at Rigshospitalet. All patients were subjected to a panel of blood tests and MR scan of the head and neck. All patients had dyspnoea at admission, and five were subjected to a combination of CO(2)-laser excision of supraglottic tissue and closure of the incision with sutures. All serological tests were negative or normal, including angiotensin 1 converting enzyme. The clinical expression was uniform with pale, smooth swellings of the supraglottic structures. Surgery proved successful to maintain normal breathing. None of the many parameters examined--some previously having been found to be abnormal in sarcoidosis--were abnormal in the present cohort. We are therefore unable to elucidate the pathogenesis. The combined surgical approach re-established normal airway function for all five patients and complete remission without further swellings was seen in two patients.