Laryngectomy plus postoperative radio(system)therapy versus primary radio(system) therapy for the treatment of locally advanced laryngeal and hypopharyngeal cancer - results from the University Clinical Cancer Registry Regensburg.

BACKGROUND: There are few adequate randomized clinical trials directly comparing the therapeutic options of primary laryngectomy (pLE) vs. primary radio(system)therapy (pR(S)T) in patients with locally advanced laryngeal and hypopharyngeal carcinoma and thus little clear scientific evidence to decide which patients will benefit most from which procedure. AIMS/OBJECTIVES: Aim was to compare survival between the therapeutic options and to learn from the limitations of this study, especially in the context of improved clinical assessment. MATERIAL AND METHODS: The clinical data of patients treated between January 2010 and February 2022 were obtained from the electronic database of the University Hospital Regensburg. Overall survival (OS) and progression-free survival (PFS) were compared between the treatment groups. RESULTS: The study included 193 patients (pLE n = 68, pR(S)T, n = 125). Median OS was 31.2 months and median PFS was 24.7 months with no significant difference between the treatment groups (p > .050). Patients who did not receive complete treatment as recommended by the tumor conference (n = 47, 24.4%) had a higher risk of death (p = .024). CONCLUSIONS AND SIGNIFICANCE: The results of our study are consistent with the survival data reported in the literature. More detailed systematic data in clinical routine (e.g. relevant comorbidities) are required to ensure guideline-based recommended therapy.

The effects of Phoniatric PREhabilitation in Head and Neck Cancer patients on Aspiration and Preservation of Swallowing (PREHAPS): study protocol of a monocentric prospective randomized interventional outcome-blinded trial.

BACKGROUND: Dysphagia, with its negative impact on life expectancy and quality of life, is a major side effect of head and neck squamous cell carcinoma (HNSCC). In a typical Head and Neck Cancer Center, more than half of patients are affected. Improving treatment, and ideally prevention respectively prehabilitation, therefore seems more than desirable. METHODS: The study is planned as a monocentric, prospective, outcome-blinded, randomized interventional study comparing an advanced phoniatric-logopedic prehabilitation with a control (standard of care). Seventy patients (30 control group, 30 intervention group, 10 drop-out rate of 15%) with an initial diagnosis of invasive HNSCC and curative treatment intention will be included over a period of 17 months. In addition to the previous standard, both groups will undergo both detailed subjective assessment of swallowing function and quality of life by means of various questionnaires and objective analyses by bioelectrical impedance measurements and phoniatric endoscopic swallowing examinations. In the intervention group, risk-related nutritional counseling (face-to-face) and phoniatric-logopedic prehabilitation are provided: detailed counseling with video demonstration and exercises to strengthen and improve the range of motion of the oral, pharyngeal, and laryngeal muscles (guided by exercise diary). Controls are performed at 6 weeks, 3 and 6 months, and 9 or 12 months after the end of therapy during the regular tumor follow-up. Primary study endpoints are swallowing function and emotional distress at 6 weeks of control visit. DISCUSSION: Prehabilitation measures have already proven successful in other patient groups, e.g., transplant patients. In the field of head and neck oncology, interest in such concepts has increased significantly in recent years. However, usually, only subgroups, e.g., patients with swallowing problems after radiochemotherapy alone, are in focus. Our study aims to investigate the general benefit of prehabilitation with regard to swallowing function, which is so important for protection of aspiration and quality of life. TRIAL REGISTRATION: German Clinical Trials Register DRKS00029676 . International Clinical Trials Registry Platform DRKS00029676 . Registered on 19 July 2022.

Head and neck oncology management in the time of COVID-19: results of a head and neck cancer center.

PURPOSE: Given the concerns about the effects of the COVID-19 pandemic on cancer care, we analyzed the treatment quality of the head and neck cancer center Regensburg before and throughout 2 years of the pandemic. We included data of 3 years to reflect the extended pandemic period as new developments continued to influence its course. METHODS: This retrospective review included all patients diagnosed with head and neck cancer in 2019, 2020, and 2021 who had not started treatment elsewhere prior to being referred to the head and neck cancer center. We compared tumor characteristics and times to therapy of patients diagnosed before COVID-19 in 2019 (n = 253), during COVID-19 in 2020 (n = 206), and in a phase of partial normalization in a persistent pandemic situation in 2021 (n = 247). RESULTS: Our data revealed no decrease in diagnoses or drift in stages toward more advanced stages. There was an increased percentage of diagnoses confirmed at the head and neck cancer center from 2019 (57.3%) to 2020 (68.0%) and to 2021 (65.6%) compared to confirmation at other institutions (2019, 42.7%; 2020, 32.0%; 2021, 34.4%; P = 0.041). Surgery and radiotherapy were performed with the same frequency. The median days between diagnosis and surgery were decreased in 2020 (19.5 days; P = 0.049) and 2021 (20.0 days; P = 0.026) in comparison to 2019 (23 days). The days to radiotherapy were not affected. CONCLUSION: The data indicate a consistent oncological performance for head and neck cancer patients in all waves of the pandemic and thereafter without a decrease in diagnoses or shift in stages.

Head and Neck Ultrasound - EFSUMB Training Recommendations for the Practice of Medical Ultrasound in Europe.

Different surgical and medical specialists increasingly use head and neck ultrasound and ultrasound-guided interventions as part of their clinical practice. We need to ensure high quality and standardized practice across specialties, and this position paper of the European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB) describes the training requirements for head and neck ultrasound. Traditionally, a minimum number of ultrasound examinations indicates competence, but this is unreliable, and a general shift towards competence-based training is ongoing. For each EFSUMB level, we will outline the theoretical knowledge and skills needed for clinical practice. The recommendations follow the three EFSUMB competency levels for medical ultrasound practice. Level 1 describes the skills required to perform essential head and neck ultrasound examinations independently, level 2 includes ultrasound-guided interventions, while level 3 involves the practice of high-level neck ultrasound and use of advanced technologies. Our goal is to ensure high quality and standardized head and neck ultrasound practice performed by different clinical specialists with these recommendations.

PD-L1 Expression and Immune Cell Infiltration in Gastroenteropancreatic (GEP) and Non-GEP Neuroendocrine Neoplasms With High Proliferative Activity.

The potential of neuroendocrine neoplasms (NEN) to respond to checkpoint inhibitors is largely unknown and full of great expectations. Immunohistochemical (IHC) studies of programmed cell death ligand 1 (PD-L1) expression in the tumor microenvironment and its implications in predicting the response to checkpoint inhibition is a very active subject. Currently, the combined analysis of PD-L1 expression and tumor-associated immune cell (TAIC) infiltration is considered the best predictive marker of therapeutic response. Here we investigated the expression of PD-L1 on tumor cells (TC) and tumor-infiltrating immune cells (IC) by IHC in 68 NEN samples with a high proliferation rate (Ki-67 >20%) from 57 patients and in 22 samples we correlated it with TAIC density by assessing intratumoral infiltration of CD3+, CD8+, and CD68+ cells. Furthermore, the tumor microenvironment was evaluated according to the classification of Teng et al. We detected PD-L1 expression in 31.6% of NEN G3. Its expression usually was weak and more IC than TC expressed PD-L1. The proportion of tumors positive for PD-L1 was comparable in NEN from different sites of origin but varied depending on tumor differentiation and disease extension. No positive IHC staining was found in 3 well-differentiated neuroendocrine tumors (NETs) with a proliferation rate above 20% (NET G3). When analyzing TAIC, we rarely (18.2%) detected intratumoral CD8+ cells, whereas infiltration by CD3+ and CD68+ cells was more common (45.5 and 59.1%, respectively). By combining CD3+ cells and PD-L1 status, we identified the immune ignorant phenotype of tumor microenvironment as being the most common phenotype, supporting the concept of a preferably combined immunotherapeutic approach in neuroendocrine carcinoma (NEC).

Interrater Reliability of Ultrasound in the Diagnosis of Sialolithiasis.

PURPOSE: The aim of this study was to assess the interrater reliability of ultrasound for diagnosing sialolithiasis. MATERIALS AND METHODS: A total of 100 consecutive patients with signs of obstructive sialadenopathy were evaluated. The patients all underwent ultrasound examinations in a standardized manner conducted by one specialist with extensive experience in the management of salivary gland disorders and proficiency in head and neck ultrasonography. The video recordings were sent to six colleagues with comparable experience without providing any further information about the patients' medical history and physical examination. RESULTS: The overall agreement between the seven observers was substantial, with a κ of 0.765 for the 100 cases and a percentage agreement level of 88.29 ±â€Š3.01 % (range: 83-94 %). The range of agreement on this video set for observer pairs varied from substantial to almost perfect agreement (0.663 to 0.878). Among the few false-negative findings (5.4 %), 71.8 % were due to distal sialolithiasis. Two-thirds of the false-positive findings (3.7 %) were due to fibrotic stenosis. CONCLUSION: The study confirmed the diagnostic value of ultrasound in sialolithiasis and demonstrated a very high level of interrater agreement, even in the absence of additional clinical patient information, thus further underscoring the importance of ultrasound as the examination of first choice in sialolithiasis.

Long-term Outcome for Open and Endoscopically Resected Sinonasal Tumors.

OBJECTIVE: Endoscopic resection of sinonasal cancer has become an alternative to open craniofacial surgery and leads to safe and satisfying results in emerging numbers. Randomized study data comparing outcomes between approaches are missing. Hence, it remains unclear which subgroups of patients might profit most from each technique. We aimed to identify such patient and tumor characteristics and gather information for future prospective study design. STUDY DESIGN: Case series with chart review. SETTING: Tertiary academic center. SUBJECTS AND METHODS: This study is based on a retrospective chart review of 225 patients undergoing open craniofacial or endoscopic resection for sinonasal malignancy between 1993 and 2015 at Munich University Hospital. Statistical analyses include t test, chi-square, Kaplan-Meier charts, and univariate and multivariate analyses. RESULTS: The sample size was similar between the endoscopic and open surgery groups. Tumors were significantly larger in patients who underwent open craniofacial resection. The risk of notable bleeding ( P = .041) was lower and hospital stay shorter ( P = .001) for endoscopic interventions of all tumor stages. Rates of overall ( P = .024) and disease-specific ( P = .036) survival were significantly improved for endoscopic cases; improved recurrence-free survival rates did not achieve statistical significance ( P = .357). For cases matched for tumor size, this improvement was confirmed for T3 tumors ( P = .038). Regional and distant metastatic tumor spread generally worsened survival in both surgical subgroups. Multivariate Cox regression analysis revealed independent prognosticators for overall survival. CONCLUSION: Endoscopic tumor resection remains a suitable option for distinct indications and showed improved outcome in intermediate-stage tumors in our collective. Further randomized studies acknowledging the here-identified factors are needed to improve future therapy guidelines and patient care.

Therapy Testing in a Spheroid-based 3D Cell Culture Model for Head and Neck Squamous Cell Carcinoma.

Current treatment options for advanced and recurrent head and neck squamous cell carcinoma (HNSCC) enclose radiation and chemo-radiation approaches with or without surgery. While platinum-based chemotherapy regimens currently represent the gold standard in terms of efficacy and are given in the vast majority of cases, new chemotherapy regimens, namely immunotherapy are emerging. However, the response rates and therapy resistance mechanisms for either chemo regimen are hard to predict and remain insufficiently understood. Broad variations of chemo and radiation resistance mechanisms are known to date. This study describes the development of a standardized, high-throughput in vitro assay to assess HNSCC cell line's response to various therapy regimens, and hopefully on primary cells from individual patients as a future tool for personalized tumor therapy. The assay is designed to being integrated into the quality-controlled standard algorithm for HNSCC patients at our tertiary care center; however, this will be subject of future studies. Technical feasibility looks promising for primary cells from tumor biopsies from actual patients. Specimens are then transferred into the laboratory. Biopsies are mechanically separated followed by enzymatic digestion. Cells are then cultured in ultra-low adhesion cell culture vials that promote the reproducible, standardized and spontaneous formation of three-dimensional, spheroid-shaped cell conglomerates. Spheroids are then ready to be exposed to chemo-radiation protocols and immunotherapy protocols as needed. The final cell viability and spheroid size are indicators of therapy susceptibility and therefore could be drawn into consideration in future to assess the patients' likely therapy response. This model could be a valuable, cost-efficient tool towards personalized therapy for head and neck cancer.

Chelidonium majus and its effects on uterine contractility in a perfusion model.

OBJECTIVE: The herbal agent celandine is thought to have mainly spasmolytic effects, but in the uterus it is regarded as promoting contractions, which can offer promising and innovative options for optimizing artificial reproduction. The aim of the present study was to investigate the effect of celandine on the uterine muscle, using a perfusion model of swine uteri. STUDY DESIGN: Sixteen swine uteri were perfused with Krebs-Ringer solution. Celandine (Chelidonium, Paverysat; Johannes Bürger Ysatfabrik Ltd., Bad Harzburg, Germany) was administered at increasing dosages. Intrauterine pressure (IUP) was recorded using an intrauterine double-chip microcatheter (Urobar 8 DS-F, Raumedic, Rehau AG & Co., Rehau, Germany). Differences in pressure (ΔP) and area under the curve (ΔAUC) after drug administration in the uterine body and uterine horn in the various dilution series were noted. A paired Student's t-test was used to evaluate differences between groups, with significance set at P<0.05. RESULTS: A significant initial increase in uterine activity was visible at each dosage. Inhibition of uterine activity was seen over longer periods of 5 and 10 min, particularly for a medium-dose range of 1-2mg/ml. At a dosage of 2mg/ml in particular, celandine almost always led to significant values. CONCLUSION: Following intra-arterial administration in a swine uterus perfusion model, celandine initially causes a significant increase in contractility, which is followed over time by a relaxation phase. This suggests interesting hypotheses on whether Chelidonium majus might be used to promote targeted sperm transport.

Primary surgical treatment of T2 oropharyngeal carcinoma.

BACKGROUND: The optimal management of oropharyngeal carcinoma (OPC) is not yet proven. The aim of this study is to analyze the outcome of primary surgical management of T2 cancers of the oropharynx. METHODS: All patients treated with primary surgery for pT2 OPCs between 1984 and 2005 were evaluated retrospectively. Two hundred and twenty eight cases were assessed for disease-specific survival (DSS) as well as local control (LC) estimates, with respect to tumor location, surgical technique, status of surgical margins, N classification, and adjuvant therapy. Cases were also evaluated for major complications and functional results. RESULTS: DSS was 73.2% and LC 88.9%. Carcinoma of the tonsils showed a significantly better DSS than lesions of the base of the tongue (DSS = 76.3 vs. 60.2%, P = 0.02). DSS estimates in patients with pN0-1 classification were significantly better in comparison with pN2-3 (83.6 vs. 64.5%, P = 0.018). Patients who were given adjuvant treatment had a better prognosis. The incidence of occult neck metastases was 17% and complications rate 12.7%. CONCLUSIONS: Primary surgical treatment of T2 OPC proved to be an effective treatment modality with a low rate of complications and satisfactory functional results. Complete tumor excision is essential and a neck dissection is justified. Most patients need adjuvant radiotherapy.