The role of elective neck dissection in T1 and T2 nasal cavity squamous cell carcinomas.

PURPOSE: To evaluate the role of elective neck dissection (END) on oncological outcome in early-stage nasal cavity squamous cell carcinomas (SCCs). METHODS: In total, 87 patients with T1 (n = 59; 67.8%) and T2 (n = 28; 32.2%) SCCs were evaluated regarding performance of END, regional recurrences (RR) and its impact on cancer-specific survival (CSS). We further created a risk score based on T-classification, tumor subsite and grading to identify patients whom may benefit from END and calculated the corresponding numbers needed to treat (NNT) to prevent RR. RESULTS: Nine (10.3%) patients experienced RR of whom 3 (5.1%) were T1 and 6 (21.4%) T2 tumors (p = 0.042). All RR originated from moderately or poorly differentiated (G2-G3) SCCs of the nasal septum or vestibule. END was done in 15 (17.2%) patients and none of those experienced RR (p = 0.121). Onset of RR represented the worst prognostic factor for CSS (HR 23.3; p = 0.007) with a 5y-CSS of 44.4% vs. 97.3% (p < 0.001). RR occurred in none of the patients with no or low risk scores compared to 31.6% (6/19) in patients with high-risk scores (p = 0.006). Accordingly, three high-risk patients would need to undergo END (NNT 2.63) to prevent RR compared to a NNT of 8 for the whole cohort. CONCLUSIONS: Although rare, occurrence of RR significantly deteriorates outcome in early stage nasal cavity SCCs, which could be effectively reduced by performance of END. The importance of END is currently underestimated and our proposed risk score helps identifying those patients who will benefit from END.

[Role of Robotic Surgery in ENT]. / Bedeutung der transoralen robotischen Chirurgie in der HNO.

Since the beginning of the 21st century, surgical robots have been used in the ENT-environment. They primarily support surgeons in minimal invasive transoral operations, especially in multidisciplinary treatment concepts of head and neck tumors, but also in snoring surgery the robot provides a complement to the established transoral laser surgery. In the meantime there is a large number of data that deals with the importance of oncological results, function maintenance, economics and future perspectives.Operation areas of the current robot devices are still limited in the ENT-environment. As the number of cases are small, efforts are being made to connect centres on a national and international level. Thus, uniform training standards, targeted knowledge and data exchange as well as further development of systems would be managed better. The creation of small and agile ENT-specific equipment could expand the possibilities as a next step for the future and finally lead to a wide scale of ENT-surgical applications.

[Planning and design of European prospective randomized trial on the value of drain in parotidectomy]. / Vorstellung einer europaweiten prospektiven Studie zur Wertigkeit einer Drainage bei Parotidektomie.

INTRODUCTION: There are no valid clinical studies on the value of wound drains in parotid surgery. The aim of the current trial is to analyze the influence of the closed wound drain (redon) on the incidence of postoperative complications such as bleeding, wound healing problems, infection, as well as salivary cyst and fistula after superficial or partial parotidectomy. METHODS: A European-wide multicenter prospective randomized study was planned. The study protocol was prepared by the leading study center (ENT University Hospital Cologne) in cooperation with the ENT University Hospitals Jena and Göttingen. The calculation of the number of cases was carried out with G*Power. The study includes test persons with an indication for parotidectomy for a benign tumor without known coagulation disorder or ongoing anticoagulation. Preoperative randomization and data management is software-supported (REDCap 9.1.24, Vanderbilt University). RESULTS: The study has been approved by the leading ethics committee in 10/2019 and is open since 04/2019. Currently, nine (9) ENT hospitals are participating in the study, 6 of them in Germany and 3 in Austria. Enrollment of patients is ongoing in 7 centers. With a calculated follow-up-to-treat population of 800 test persons, the planned duration of the study is 4 years. CONCLUSIONS: The Redon-study is the first prospective randomized study worldwide to investigate the effect of a drain in parotidectomy. In order to achieve the recruitment goal within the planned time frame, the participation of further specialized study centers is needed. We also encourage all ENT physicians to make their patients aware of the Redon study, inform them about the possibility of participating in the study and refer them to one of the participating centers.

Lymph node ratio as a prognostic marker in advanced laryngeal and hypopharyngeal carcinoma after primary total laryngopharyngectomy.

BACKGROUND: We evaluated the prognostic value of lymph node ratio (LNR) in patients with advanced laryngeal and hypopharyngeal squamous cell carcinoma. STUDY DESIGN: Retrospective chart review. METHODS: Between 1994 and 2018, 79 patients underwent total laryngopharyngectomy and adjuvant therapy. LNR was determined and statistically compared to patients' overall survival (OS), disease-specific survival (DSS), disease-free survival (DFS), locoregional and distant failure. RESULTS: The 5-year OS, DSS and DFS rates were 45.6%, 73.4% and 56.9%, respectively. 24.1% and 25.3% developed loco- regional failure or distant metastatic disease, respectively. Univariate analyses showed that high LNR (cut-off >0.07) was significantly associated with distant and locoregional failure. On multivariate analysis, LNR remained an independent predictor for OS (P = .004), DSS (P = .009) and DFS (P = .044). CONCLUSION: Increased LNR in patients with advanced laryngeal or hypopharyngeal carcinoma is significantly linked to shortened OS, DSS, DFS and higher locoregional and distant metastatic disease.

Comparative Analysis of Clinical and Pathological Lymph Node Staging Data in Head and Neck Squamous Cell Carcinoma Patients Treated at the General Hospital Vienna.

BACKGROUND: Results from publications evaluating discrepancies between clinical staging data in relation to pathological findings demonstrate that a significant number of head and neck squamous cell carcinoma (HNSCC) patients are not correctly staged. The aim of this retrospective study was to analyze potential discrepancies of radiological assessment versus pathological data of regional lymph node involvement and to compare the results with data published in the literature. PATIENTS AND METHODS: In a retrospective analysis we focused on patients with HNSCC routinely treated by surgery plus postoperative radiotherapy between 2002 and 2012. For inclusion, complete pre-operative clinical staging information with lymph node status and patho-histological information on involved lymph node regions as well as survival outcome data were mandatory. We included 87 patients (UICC stage III-IV 90.8%) for which the aforementioned data obtained by CT or MRI were available. Overall survival rates were estimated by the Kaplan-Meier method. The Pearson correlation coefficient and Spearman's rank correlation coefficient (non-linear relationship) was calculated. RESULTS: Discrepancies at the level of overall tumour stage assessment were noticed in 27.5% of all cases. Thereof, 5.7% were assigned to patho-histological up-staging or down-staging of the primary tumour. At the lymph node level, 11.5% of the patients were downstaged, and 10.3% were upstaged. CONCLUSIONS: The study showed that in approximately one-fifth (21.8%) of the patients, lymph node assessment by CT or MRI differs from the pathologic staging, an outcome that corresponds well with those published by several other groups in this field.

A phase II study of bortezomib in patients with MALT lymphoma.

We have performed a phase II study to evaluate bortezomib in patients with MALT-lymphoma. Sixteen patients entered the trial, 4 had gastric MALT-lymphoma, 7 of the ocular adnexa, one of the colon, and 2 of the parotid, and one patient each the lung and the breast. Bortezomib was given at 1.5 mg/m(2) days 1, 4, 8 and 11; repeated every 21 days. The overall response rate was 80% (13/16); 7 patients achieved complete remission (43%), 6 partial response (37%) and 3 stable disease. After a median follow-up of 23 months (range; 8-26), all patients are alive and 4 have relapsed. Fifteen patients required dose reductions due to either neuropathy (7 patients) or diarrhea (8 patients). Bortezomib appears to be active in patients with MALT-lymphoma. However, an unexpectedly high rate of toxicities was seen, warranting assessment of combination schedules with bortezomib at a lower dose than given in our study.

Analysis of 60 patients after tympanotomy and sealing of the round window membrane after acute unilateral sensorineural hearing loss.

OBJECTIVE: This retrospective study was performed to evaluate the effectiveness of tympanotomy and sealing of the round window membrane after unilateral acute hearing loss. DESIGN: All patients presenting idiopathic sudden hearing loss, acoustic, or barotrauma were treated with prednisolone and caroverine. Thirty-six patients had a mean pure tone hearing level worse than 70 dB. Recovery was defined as improvement of hearing threshold for 5 frequencies (250, 500, 1000, 2000, and 4000 Hz). If hearing did not improve after conservative treatment, an exploratory tympanotomy and sealing of the round window membrane were suggested. In the last 8 years, 60 patients with idiopathic sudden hearing loss, acoustic, or barotrauma underwent tympanotomy. RESULTS: In 40 patients, we observed improvement of hearing level up to complete remission. In 20 patients, no change could be detected. In the group of patients with documented barotrauma, 12 patients showed improved hearing levels. Of 37 patients with idiopathic sudden hearing loss, 26 had an improved hearing after surgery. Most patients were operated on within 14 days (range, 1-60 days), but time of surgery had no influence on outcome in patients with idiopathic hearing loss. In contrast, in patients with barotrauma, time of surgery seems to have an influence on outcome. CONCLUSIONS: Tympanotomy and sealing of the round window membrane can be recommended in cases of acute hearing loss after failure of conservative treatment.

Nodal Metastases in Acinic Cell Carcinoma of the Parotid Gland.

The objective of this study was to evaluate the clinical outcome of patients with acinic cell carcinomas of the parotid gland after elective neck dissection (END). A retrospective chart review was performed including 66 patients with acinic cell carcinoma of the parotid gland. Clinical parameters were retrieved and statistically analyzed regarding disease-free survival (DFS) and disease-specific survival (DSS). An END was done in 27 (40.9%) patients, and occult metastases were detected in 4 (14.8%) patients of whom three were low-grade carcinoma. Positive neck nodes were associated with significantly worse DSS (p = 0.05). Intermediate and high-grade carcinoma (HR 8.62; 95% confidence interval (CI): 1.69-44.01; p = 0.010), perineural invasion (HR 19.6; 95%CI: 0.01-0.37; p = 0.003) and lymphovascular invasion (HR 10.2; 95%CI: 0.02-0.59; p = 0.011) were worse prognostic factors for DFS. An END should be considered in patients with acinic cell carcinoma of the parotid gland due to (i) a notable rate of occult neck metastases in low-grade tumors and (ii) the worse DSS of patients with positive neck nodes.

Effect of postoperative radiotherapy in pT1pN1cM0 and pT2p/cN0cM0 oropharyngeal squamous cell carcinoma.

OBJECTIVES/HYPOTHESIS: Consulting of patients with oropharyngeal carcinoma, classified as pT1pN1cM0 and pT2p/cN0cM0, about postoperative radiotherapy is a precarious task as data are lacking. The aim of this study was to evaluate the effects of postoperative radiotherapy for patients with intermediate-stage oropharyngeal carcinoma. STUDY DESIGN: Multicentric retrospective study. METHODS: This analysis was conducted at seven Austrian institutions and included data of patients treated between 2000 and 2012. A total of 81 patients with oropharyngeal squamous cell carcinoma were included, of whom 33 patients received postoperative radiotherapy. p16 status determined by immunohistochemistry was available in 68 patients. RESULTS: Median follow-up was 47.9 months. Postoperative radiotherapy showed no benefits in regard to overall survival (P = .701). In contrast, disease-free survival was significantly shortened in all patients without postoperative radiotherapy (P = .001). When dividing the cohort in dependence of p16, p16-positive patients did not benefit from postoperative radiotherapy regarding overall and disease-free survival (P = .934 and P = .102), whereas p16-negative patients showed improved disease-free survival after postoperative radiotherapy (P = .007). Multivariate analysis showed that outcome of postoperative radiotherapy is dependent on p16 status. CONCLUSIONS: In terms of disease-free survival, patients with p16-negative tumors may benefit from postoperative radiotherapy, whereas survival of p16-positive patients is good regardless of additional treatment. LEVEL OF EVIDENCE: 4. Laryngoscope, 128:1075-1082, 2018.

High relapse rate in patients with MALT lymphoma warrants lifelong follow-up.

BACKGROUND: B-cell lymphoma of the mucosa-associated lymphoid tissue (MALT lymphoma) is thought to be an indolent disease, with a good prognosis following various forms of treatment. Little, however, is known about the rate and pattern of relapse following successful treatment. PATIENTS AND METHODS: We have analyzed time to and pattern of relapse in patients with MALT lymphoma, along with investigation of t(11;18)(q21;q21), t(1;14)(p22;q32), and t(14;18)(q32;q21) involving IGH/MALT1, trisomy 3, and trisomy 18. Eighty-six patients achieving complete remission (CR) after initial therapy with sufficient follow-up data were available. Primary site of disease was the stomach (n = 36), salivary gland (n = 19), ocular adnexa/orbit (n = 12), lung (n = 8), thyroid (n = 5), breast (n = 3), liver (n = 2), and skin (n = 1). RESULTS: Thirty-two patients (37%) relapsed between 14 and 307 months (median 47 months) after initial CR. Ten relapses were local, whereas the remaining patients relapsed in a distant organ. Eight of 36 gastric versus 24 of 50 nongastric MALT lymphomas (P = 0.02) relapsed. Five patients had a second recurrence 26 to 56 months after a second CR. Relapse rates were not related to forms of initial treatment. Chromosomal aberrations were detected in 14 of 28 (50%) relapsing patients, and chromosomal alterations were identical at diagnosis and relapse. No significant association of any of the genetic changes investigated with relapse was found. Interestingly, patients with t(11;18)(q21;q21) had a significantly longer median time to relapse (76 months) than patients without this translocation (29 months; P = 0.012). CONCLUSIONS: In view of the late relapses seen in our series, lifelong observation of all patients treated for MALT lymphoma seems to be required.

Effect of postoperative use of diclofenac on pharyngocutaneous fistula development after primary total laryngopharyngectomy: Results of a single-center retrospective study.

BACKGROUND: Primary total laryngopharyngectomy is the treatment of choice in many cases of locally advanced hypopharyngeal and laryngeal cancer. Development of pharyngocutaneous fistulae is the most common postoperative complication. A recent Danish study showed significantly increased rates of anastomosal leakage after colorectal resection in patients receiving diclofenac treatment. METHODS: We retrospectively analyzed 67 patients after primary total laryngopharyngectomy to determine whether diclofenac increases the risk for development of pharyngocutaneous fistula analogously to leakage in the colorectal area. RESULTS: The fistula rate in the total study population (n = 67) was 19.4%. In the group receiving diclofenac postoperatively (n = 31), the fistula rate was 25.8%. In the patient group not receiving diclofenac (n = 36), the fistula rate was 13.9% (p = .219). CONCLUSION: Our results suggest that cyclooxygenase-2 (COX-2) selective nonsteroidal anti-inflammatory drugs (NSAIDs) should be administered with caution after laryngopharyngectomy. Additional studies on larger cohorts are required to further evaluate our findings. © 2015 Wiley Periodicals, Inc. Head Neck 38: E1515-E1520, 2016.

Electroporation therapy in head and neck cancer.

OBJECTIVE: To prove the efficacy of electroporation therapy (EPT) in T1 and T2 squamous cell cancers of the oral cavity and oropharynx. MATERIAL AND METHODS: Twelve patients were treated with EPT within the framework of a European trial. Tumors were infiltrated with a bleomycin solution and subsequently treated with EPT. Four weeks after treatment the necrotic mass at the site of the former tumor was resected with save margins and accurately examined histologically. RESULTS: Whereas 10 specimens were completely free of cancer cells, 2 cases showed viable tumor cells. CONCLUSION: EPT has the potential to serve as an interesting alternative in the treatment of head and neck cancer.

Ethanol decreases negative cell-cycle-regulating proteins in a head and neck squamous cell carcinoma cell line.

Epidemiologic studies have provided evidence of an alcohol-associated increased risk of upper aerodigestive tract cancers. Recently we reported ethanol-induced proliferation in a squamous cell carcinoma of the head and neck (SCCHN) cell line, but the underlying mechanisms are unknown. In order to further clarify these findings, major G0/G1-regulating proteins were investigated in the present study. Synchronized cells of a SCCHN line (JP-PA) and a human immortalized keratinocyte line (HaCaT)-used as a control-were cultured with or without 10(-3) M ethanol for up to 96 h. At distinct time intervals the expression of cyclin D1 and the inhibitors p16, p18, p19 and p21 were determined by Western blot analyses. In both lines ethanol had no influence on the protein expression of cyclin D1. In contrast, distinct downregulations of p21, p18 and p19 were detectable at the protein level. The p16 protein was not expressed in the SCCHN line and was unchanged in the control line after the addition of ethanol. In these in vitro experiments the marked downregulation of important cell-cycle inhibitors may accelerate progression from the G1 to the S phase of the cell cycle. The relevance of our findings to in vivo conditions remains speculative, but the observed mechanisms of significantly reduced expression of cell-cycle inhibitor proteins may be involved in the carcinogenesis of head and neck malignancies.

Molecular analysis of p21 promoter activity isolated from squamous carcinoma cell lines of the head and neck under the influence of 1,25(OH)2 vitamin D3 and its analogs.

OBJECTIVE: The biologically active 1,25(OH)2 vitamin D3 and its analogs have been shown to have antiproliferative and differentiating effects in a variety of malignant and non-malignant cells. For squamous carcinoma cell lines of the head and neck (SCCHN) we could show that this antiproliferative activity of 1,25(OH)2 vitamin D3 is due to induced expression of the cell-cycle inhibitory proteins p21 and p27, causing an arrest in the G0/G1 cell-cycle phase. MATERIAL AND METHODS: In this work we investigated the effects of three vitamin D3 analogs, EB1089, MC1288 and CB1093, on proliferation behavior and cell-cycle status in a laryngeal carcinoma cell line (JPPA) as well as in control human immortalized keratinocytes (HaCaT). To study the molecular mechanism the functional activity of the promoter region of p21, a potential target gene of vitamin D3 transcriptional regulation, was investigated. For this reason a 2.7-kb fragment of the p21 promoter was isolated by polymerase chain reaction from HaCaT, JPPA and SCC9 (tongue carcinoma) cells and directionally cloned into an enhanced green fluorescence protein (EGFP) reporter gene vector system. A construct was used to stably transfect HaCaT cells and to monitor the expression of the EGFP gene by confocal microscopy. RESULTS: Analysis of proliferation and cell-cycle status revealed decreased growth rates and G0/G1I cell-cycle arrest in cells treated with 1,25(OH)2 vitamin D3 and its analogs The EGFP reporter gene-transfected cells showed distinct fluorescence under the influence of 1,25(OH)2 vitamin D3 and its analogs compared to control cells. CONCLUSION: These results demonstrate that the cell-cycle inhibitor protein p21 is a direct target gene of biologically active 1,25(OH)2 vitamin D3, inducing G0/G1 cell-cycle arrest. The ability of vitamin D analogs to act via the same molecular mechanism as the natural hormone but with less hypercalcemic activity may have therapeutic implications for patients with SCCHN malignancy.

Vestibular symptoms as a complication of sildenafil: a case report.

Potential vasodilator side effects of sildenafil such as headache, flushing, dyspepsia, heartburn, nasal congestion, dizziness and visual changes have been frequently observed. We report a 79-year-old man who developed severe vestibular neuritis-like symptoms (horizontal nystagmus with rotatory components and vomiting) two hours after taking 50 mg sildenafil. Additionally, the patient complained of tinnitus in both ears. Internal and neurological examination revealed no pathological findings and the patient had no history of cardiovascular disease. The symptoms lasted for 24 hours and then resolved completely. All of the patient's complaints indicated a drug-related phenomenon. This drug related adverse reaction should be included in the long list of potential side effects of sildenafil.

Clinicopathological aspects of mucosa-associated lymphoid tissue (MALT) lymphoma of the parotid gland: a retrospective single-center analysis of 28 cases.

BACKGROUND: In contrast to its gastric counterpart, mucosa-associated lymphoid tissue (MALT) lymphoma of the parotid gland has not been studied extensively. We analyzed the clinicopathological features and the clinical course of all patients with parotid gland MALT lymphoma diagnosed and treated at our institution. METHODS: Patient characteristics including an underlying autoimmune disease, disease stage, genetic aberrations, treatment, and clinical course were assessed and evaluated. Twenty-eight patients (19 women, 9 men) were identified; median age at diagnosis was 49 years (interquartile range [IQR], 40-56), and 18 patients (64%) had an underlying autoimmune disease. Eleven had stage IE, 7 patients had stage IIE, and 10 had advanced disease (stage IV). RESULTS: Genetic aberrations were detected in 9 of 20 patients; 5 patients had trisomy 3, 2 patients had a t(11;18)(q21;21) translocation, 1 had trisomy 3 and 18, and 1 patient had a t(14;18)(q32;q21) translocation plus trisomy 18. After a median follow-up time of 62 months (IQR, 32-98 months), 24 patients (86%) are alive. Fifteen patients are free from lymphoma, whereas 13 patients (46%) have had a relapse. CONCLUSION: Our data suggest that MALT lymphoma of the parotid gland is often associated with autoimmune diseases and that trisomy 3 is the most common genetic feature of this disease. The high rate of relapse warrants further study on optimal therapy of such patients.

[Treatment of salivary gland malignancies]. / Therapie von Speicheldrüsenmalignomen.

Salivary gland carcinomas comprise a rare group of malignant tumors which are characterized by their histopathological diversity, variable clinical course, in particular with respect to the facial nerve. Surgical resection with or without adjuvant radiotherapy is the treatment of choice. Surgical procedures are depending on the pathohistological diagnosis and the clinical staging according to the TNM classification respectively. The present paper gives a short overview about the therapeutic modalities with malignant tumors of the salivary glands.

[Follow up in head and neck cancer]. / Nachsorge bei Kopf-Hals-Karzinomen.

Some principle questions rise in follow up of tumour patients: Is there a chance to detect tumour recurrence or a second primary early enough to give the patient reasonable options of cure or at least lead to a better survival? What means will be necessary to achieve this goal? Do the means justify the outcome? This paper determines and compares current regimens and strategies in the follow up of head and neck cancer patients. It stresses not only the questions stated above, but also stresses additional points of view in the follow up like speech and swallow rehabilitation, as well as social reintegration and psychological support of head and neck tumour patients. Standard follow up includes facilities for speech and swallow rehabilitation. Summarizing the literature follow up mainly is based on the clinical examination and the work up of the recent medical history. Since most relapses occur within the first two years, recommendation of visit-intervals is every two months, range should be risk-adapted. Up to now there is no evidence for better overall survival using sumptuous means like repeated panendoskopies, laboratory parameters, CT's, MRIs or PETs for detecting disease relapse in the asymptomatic patient. In high risk cancer patients the intervals will be shortened compared to the average schedule recommended. Additional tests will be initiated on demand only. Since clinical evaluation of symptoms in head and neck cancer patients is difficult to assess there is an increased responsibility with respect to the indication for extended diagnostic work up. Therefore this should be reserved for well equipped and highly trained ENT Oncologists.

Prognostic value of T-cell receptor gamma rearrangement in peripheral blood or bone marrow of patients with peripheral T-cell lymphomas.

Peripheral T-cell lymphomas (PTCL) have a variable outcome. We have investigated the prognostic value of molecular staging in non-anaplastic PTCL. T-cell receptor gamma rearrangements were routinely determined in peripheral blood (n = 40) and bone marrow (n = 38) of patients with PTCL (75% unspecified) by conventional PCR at diagnosis. Tissue controls for PCR included 24 tumour biopsies. Twenty-four patients (60%) had a PCR-detectable clonal TCR gamma rearrangement in PB or BM. These TCR gamma PCR positive patients had significantly more stage IV disease (14 patients of 15 patients; P = 0.001), elevated LDH (14 of 18 patients; P = 0.04), higher IPI (16 of 21 patients; P = 0.03), more anemia (15 of 19 patients; P = 0.02) and lower platelet counts (seven of seven patients; P = 0.02). Clinical outcome of this clonal group was characterised by lower complete remission rates (37.5% vs. 62.5%), and overall response rates (58.3% vs. 87.5%; P < 0.05) as well as a significantly shorter median overall survival (12.8 vs. 30.0 months; P = 0.006). Patients with clinical stages I - III but molecular stage IV had an equally poor overall survival when compared with patients with clinical stage IV (15.8 vs. 13.9 months). In contrast, patients with CS I - III in the absence of a TCR gamma rearrangement in PB or BM had a favourable outcome with an estimated overall survival of 70% at 3 and 5 years. Molecular staging in PB and BM by TCR gamma PCR at diagnosis may serve as a useful prognostic tool in PTCL.