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Background: Resection margins are an important prognostic factor for patients with head and neck cancer. In general, for head and neck surgery, a margin >5 mm is advised by the Royal College of Pathologists. However, this cannot always be achieved during laryngeal and hypopharyngeal surgery. The aim of this study is to identify the resection surfaces and measure the maximum feasible margins per subsite. The clinical relevance of these maximum feasible resection margins were analyzed in this descriptive anatomical study., Methods: head and neck surgeons and a pathologist from the Erasmus MC performed a total laryngectomy and laryngopharyngectomy on a head and neck specimen specifically available for research., Results: For a total laryngectomy, resection margins >5 mm were not feasible for the ventral and dorsal resection surface. For a total laryngopharyngectomy, resection margins >5 mm were not feasible for the ventral, dorsal and lateral resection surface., Conclusion: Clear resection margins, defined as a margin >5 mm, are not always feasible in laryngeal and hypopharyngeal surgery, due to the anatomy of the larynx and tumor location. However, striving for a maximum feasible margin is still the main goal. We propose a new guideline for maximum feasible but adequate resection margins in larynx and hypopharynx tumor surgery.

Background: Laryngeal and hypopharyngeal cancer is complex and resection margins are therefore constrained. The aim of this study was to investigate the clinical relevance of resection margins in laryngeal and hypopharyngeal surgery., Methods: A retrospective cohort study was performed for patients treated with a total laryngectomy (TL) or laryngopharyngectomy (TLP) for laryngeal or hypopharyngeal squamous cell carcinoma (LSCC and HSCC, respectively). Within the groups primary LSCC, recurrent LSCC, primary HSCC, and recurrent HSCC the relationship between the status of the resection margin according to the Royal Collage of Pathology and the recurrence and survival rates were investigated., Results: Positive resection margins were found in 54% for primary LSCC, 29% for recurrent LSCC, 62% for primary HSCC, and 44% for recurrent HSCC. For primary and recurrent LSCC, there was a linear association between total recurrence and narrowing margins ( p = 0.007 resp. p = 0.008). Multivariate survival analysis for primary and recurrent LSCC showed a significantly worse disease free and disease-specific survival in case of positive margins compared to clear margins., Conclusion: Similar survival rates were recorded for close and clear margins for primary and recurrent LSCC. This may suggest that a margin > 5 mm is not clinically relevant in terms of survival. Therefore, a margin of 1-5 mm should be accepted in certain subsites. Margins < 1 mm are related to significantly worse outcomes and should be avoided.

Background: Patients with head and neck squamous cell carcinoma (HNSCC) can develop second primary tumors (SPTs) in the esophagus. Endoscopic screening could lead to detection of SPTs at early stages and improve survival., Methods: We performed a prospective endoscopic screening study in patients with curably treated HNSCC diagnosed between January 2017-July 2021 in a Western country. Screening was performed synchronously (< 6 months) or metachronously (≥ 6 months) after HNSCC diagnosis. Routine imaging for HNSCC consisted of flexible transnasal endoscopy with positron emission tomography/computed tomography or magnetic resonance imaging, depending on primary HNSCC location. The primary outcome was prevalence of SPTs, defined as presence of esophageal high grade dysplasia or squamous cell carcinoma., Results: 202 patients (mean age 65 years, 80.7 % male) underwent 250 screening endoscopies. HNSCC was located in the oropharynx (31.9 %), hypopharynx (26.9 %), larynx (22.2 %), and oral cavity (18.5 %). Endoscopic screening was performed within 6 months (34.0 %), 6 months to 1 year (8.0 %), 1-2 years (33.6 %), and 2-5 years (24.4 %) after HNSCC diagnosis. We detected 11 SPTs in 10 patients (5.0 %, 95 %CI 2.4 %-8.9 %) during synchronous (6/85) and metachronous (5/165) screening. Most patients had early stage SPTs (90 %) and were treated with curative intent with endoscopic resection (80 %). No SPTs in screened patients were detected with routine imaging for HNSCC before endoscopic screening., Conclusion: In 5 % of patients with HNSCC, an SPT was detected with endoscopic screening. Endoscopic screening should be considered in selected HNSCC patients to detect early stage SPTs, based on highest SPT risk and life expectancy according to HNSCC and comorbidities., Competing Interests: The authors declare that they have no conflict of interest., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/).)

Patients with oral cavity cancer are almost always treated with surgery. The goal is to remove the tumor with a margin of more than 5 mm of surrounding healthy tissue. Unfortunately, this is only achieved in about 15% to 26% of cases. Intraoperative assessment of tumor resection margins (IOARM) can dramatically improve surgical results. However, current methods are laborious, subjective, and logistically demanding. This hinders broad adoption of IOARM, to the detriment of patients. Here we present the development and validation of a high-wavenumber Raman spectroscopic technology, for quick and objective intraoperative measurement of resection margins on fresh specimens. It employs a thin fiber-optic needle probe, which is inserted into the tissue, to measure the distance between a resection surface and the tumor. A tissue classification model was developed to discriminate oral cavity squamous cell carcinoma (OCSCC) from healthy oral tissue, with a sensitivity of 0.85 and a specificity of 0.92. The tissue classification model was then used to develop a margin length prediction model, showing a mean difference between margin length predicted by Raman spectroscopy and histopathology of -0.17 mm.

Background: Immunoglobulin G4-related disease (IgG4-RD) is a fibro-inflammatory disorder and manifestation in de paranasal and sphenoid sinus is well recognized. In this patient, IgG4-RD presented in an unusual manner with vision loss due to mucocele formation in the sphenoid sinus., Case Description: A 19-year-old man, with an unremarkable medical history, was referred with decreased vision in the left eye, headaches, and a sharp pain in the left orbit and ear. Compression of the left optic nerve due to a large mucocele caused papillary edema and emergency endoscopic marsupialization of the mucocele was performed. When the vision decreased again, a more extensive decompressing sphenoidotomy was performed. Histopathology showed IgG4-RD. Despite dexamethasone, the lesion expanded to the anterior skull base and the patient required repeat endoscopic surgery. After 3 months, a decrease in smell and vision warranted for a fourth extensive endoscopic decompressing surgery, complicated by a cerebrospinal fluid leak. Prednisone and later rituximab were commenced. Unfortunately, the patient reported a complete loss of vision after 4 months of rituximab due to increased mass effect on the optic nerve. An extensive combined craniofacial-endoscopic surgery was performed to remove the entire mucocele and to prevent further contralateral and intracranial progression. Methylprednisolone monthly was commenced to prevent further complications., Discussion: This case illustrates that in therapy-resistant sino-orbital IgG4-RD, extensive surgery might be necessary at an earlier stage. It may even be the only option to prevent irreversible damage to the surrounding tissues. A multidisciplinary approach in the management of sino-orbital IgG4-RD is therefore warranted., (© 2022 The Authors. International Forum of Allergy & Rhinology published by Wiley Periodicals LLC on behalf of American Academy of Otolaryngic Allergy and American Rhinologic Society.)

Introduction: A challenge in the treatment of patients with head and neck cancer is the management of occult cervical lymph node (LN) metastases. Single-fiber reflectance (SFR) spectroscopy has the potential to detect physiological tissue changes that occur in a positive LN. This pilot study aimed to investigate whether SFR spectroscopy could serve as an alternative or additional technique to detect cervical lymph node metastases., Materials and Methods: We performed intraoperative SFR spectroscopy measurements of LNs with and without malignancies. We analyzed if physiological and scattering parameters were significantly altered in positive LNs., Results: Nine patients with a total of nineteen LNs were included. Three parameters, blood volume fraction (BVF), microvascular saturation (StO 2 ), and Rayleigh amplitude, were significantly lower in positive LNs. They were combined into one optical parameter 'delta', using discriminant analysis. Delta was significantly decreased in positive LNs, p = 0,0006. It had a high diagnostic accuracy where the sensitivity, specificity, PPV, and NPV were 90,0%, 88.9%, 90,0%, and 88.9%, respectively. The area under the ROC curve was 96.7% (95% confidence interval 89.7-100.0%)., Conclusion: This proof of principle study is a first step in the development of an SFR spectroscopy technique to detect LN metastases in real time. A next step towards this goal is replicating these results in LNs with smaller metastases and in a larger cohort of patients. This future study will combine SFR spectroscopy with fine-needle aspiration, using the same needle, to perform preoperative in vivo measurements., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Patients with head and neck squamous cell carcinoma (HNSCC) have an increased risk of developing esophageal second primary tumors (ESPTs). We aimed to determine the incidence, stage, and outcome of synchronous ESPTs in patients with HNSCC in a Western population. We performed a prospective, observational, and cohort study. Patients diagnosed with HNSCC in the oropharynx, hypopharynx, any other sub-location in combination with alcohol abuse, or patients with two synchronous HNSCCs, between February 2019 and February 2020 underwent screening esophagogastroduodenoscopy (EGD). ESPT was defined as presence of esophageal squamous cell carcinoma (ESCC) or high grade dysplasia (HGD). Eighty-five patients were included. A lesion suspected for ESPT was detected in 14 of 85 patients, which was pathologically confirmed in five patients (1 ESCC and 4 HGD). The radiotherapy field was extended to the esophagus in two of five patients, HGD was treated with endoscopic resection in three of five patients. None of the ESPTs were detected on MRI and/or CT-scan prior to EGD. Of the remaining nine patients, three had low grade dysplasia on histology whereas the other six patients had benign lesions. Incidence of synchronous ESPT was 5.9% in our cohort of HNSCC patients. All ESPTs were diagnosed at an early stage and treated with curative intent. We recommend that screening for synchronous ESPTs should be considered in a selected group of patients with HNSCC., (© The Author(s) 2021. Published by Oxford University Press on behalf of International Society for Diseases of the Esophagus. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objectives: To define metastatic categories based on their prognostic significance. We hypothesized that oligometastasis in patients with head and neck squamous cell carcinoma (HNSCC) is associated with better post-distant metastasis disease specific survival (post-DM DSS) compared to patients with polymetastasis. Furthermore, the impact on survival of synchronous versus metachronous distant metastasis (DM) occurrence was assessed., Materials and Methods: Retrospective cohort study in which patients with DM were stratified into three groups: oligometastasis (maximum of 3 metastatic foci in ≤2 anatomic sites), explosive metastasis (≥4 metastatic foci at one anatomic site) and explosive-disseminating metastasis (spread to ≥3 anatomic sites or >3 metastatic foci in 2 anatomic sites). In addition, patients were divided into synchronous versus metachronous DM., Results: Between January 1, 2006 and December 31, 2013, a total of 2687 patients with HNSCC were identified, of which 324 patients developed DM. In this group, 115 (35.5%) patients had oligometastasis, 64 (19.8%) patients had explosive metastasis and 145 (44.8%) patients had explosive-disseminating metastasis. Their median post-DM DSS were 4.7 months, 4.1 months and 1.7 months respectively (p < .001). Synchronous DM was associated with more favorable survival rates in univariable and multivariable analyses than metachronous DM with recurrence of the index tumor (6-month post-DM DSS probability of 0.51 vs 0.17, p < .001)., Conclusion: Oligometastasis in HNSCC signifies a better prognosis than a polymetastatic pattern. Metachronous DM occurrence with recurrence of the primary index tumor is associated with an unfavorable prognosis., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

The goal of head and neck oncological surgery is complete tumor resection with adequate resection margins while preserving acceptable function and appearance. For oral cavity squamous cell carcinoma (OCSCC), different studies showed that only 15%-26% of all resections are adequate. A major reason for the low number of adequate resections is the lack of information during surgery; the margin status is only available after the final histopathologic assessment, days after surgery. The surgeons and pathologists at the Erasmus MC University Medical Center in Rotterdam started the implementation of specimen-driven intraoperative assessment of resection margins (IOARM) in 2013, which became the standard of care in 2015. This method enables the surgeon to turn an inadequate resection into an adequate resection by performing an additional resection during the initial surgery. Intraoperative assessment is supported by a relocation method procedure that allows accurate identification of inadequate margins (found on the specimen) in the wound bed. The implementation of this protocol resulted in an improvement of adequate resections from 15%-40%. However, the specimen-driven IOARM is not widely adopted because grossing fresh tissue is counter-intuitive for pathologists. The fear exists that grossing fresh tissue will deteriorate the anatomical orientation, shape, and size of the specimen and therefore will affect the final histopathologic assessment. These possible negative effects are countered by the described protocol. Here, the protocol for specimen-driven IOARM is presented in detail, as performed at the institute.

Objectives: To compare the impact on survival and late radiation toxicity of patients with squamous cell carcinoma of unknown primary who were treated with ipsilateral neck dissection and ipsilateral postoperative radiotherapy (PORT) and patients treated with ipsilateral neck dissection and PORT to both sides of the neck plus the pharyngeal axis., Methods: Retrospective cohort study performed at the Erasmus University Medical Center in which 78 patients with squamous cell carcinoma of unknown primary were identified. Thirty-nine patients received PORT to both sides of the neck plus the pharyngeal axis (BILAX) and another 39 patients were irradiated on the ipsilateral neck (IPSI) only. The endpoints of the present study were 3-year overall survival (OS), 3-year disease-free survival (DFS), and overall late radiation toxicity., Results: The 3-year OS rate of the entire group of 78 patients was 74.2% and the 3-year DFS rate was 72.7%. The 3-year OS rates for the IPSI and the BILAX groups were 74.4% and 74.1%, respectively ( P = .654). The most common late radiation toxicity experienced was xerostomia (64.8%), which was significantly more often seen in the BILAX group than in the IPSI group (83.8% and 44.1%, respectively, P = .001). Overall late radiation toxicity was significantly higher in the BILAX group ( P = .003)., Conclusion: There was no significant difference in OS and DFS rates between the IPSI and the BILAX group. Late radiation toxicity was significantly higher in the BILAX group., Level of Evidence: Level 2b: Individual retrospective cohort study., Competing Interests: 6The authors declare no potential conflict of interest., (© 2021 The Authors. Laryngoscope Investigative Otolaryngology published by Wiley Periodicals LLC. on behalf of The Triological Society.)

Objective: The depth of invasion (DOI) is considered an independent risk factor for occult lymph node metastasis in oral cavity squamous cell carcinoma (OCSCC). It is used to decide whether an elective neck dissection (END) is indicated in the case of a clinically negative neck for early stage carcinoma (pT1/pT2). However, there is no consensus on the cut-off value of the DOI for performing an END. The aim of this study was to determine a cut-off value for clinical decision making on END, by assessing the association of the DOI and the risk of occult lymph node metastasis in early OCSCC., Methods: A retrospective cohort study was conducted at the Erasmus MC, University Medical Centre Rotterdam, The Netherlands. Patients surgically treated for pT1/pT2 OCSCC between 2006 and 2012 were included. For all cases, the DOI was measured according to the 8 th edition of the American Joint Committee on Cancer guideline. Patient characteristics, tumor characteristics (pTN, differentiation grade, perineural invasion, and lymphovascular invasion), treatment modality (END or watchful waiting), and 5-year follow-up (local recurrence, regional recurrence, and distant metastasis) were obtained from patient files., Results: A total of 222 patients were included, 117 pT1 and 105 pT2. Occult lymph node metastasis was found in 39 of the 166 patients who received END. Univariate logistic regression analysis showed DOI to be a significant predictor for occult lymph node metastasis (odds ratio (OR) = 1.3 per mm DOI; 95% CI: 1.1-1.5, p = 0.001). At a DOI of 4.3 mm the risk of occult lymph node metastasis was >20% (all subsites combined)., Conclusion: The DOI is a significant predictor for occult lymph node metastasis in early stage oral carcinoma. A NPV of 81% was found at a DOI cut-off value of 4 mm. Therefore, an END should be performed if the DOI is >4 mm., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Aaboubout, van der Toom, de Ridder, De Herdt, van der Steen, van Lanschot, Barroso, Nunes Soares, ten Hove, Mast, Smits, Sewnaik, Monserez, Keereweer, Caspers, Baatenburg de Jong, Bakker Schut, Puppels, Hardillo and Koljenović.)

Objectives: Depth of invasion (DOI) is the most important predictor for lymph node metastasis (LNM) in early stage (T1-T2) oral cancer. The aim of this study is to validate the cut-off value of 4 mm on which the decision to perform an Elective Neck Dissection (END) is made., Materials and Methods: We performed a retrospective study in patients with pathologically proven early stage oral cavity squamous cell carcinoma (OCSCC) without clinical or radiological signs of LNM, who were treated between 2013 and 2018. An END was performed when DOI was ≥ 4 mm and a watchful waiting protocol was applied in patients with DOI < 4 mm., Results: Three hundred patients were included. END was performed in 77% of patients with DOI ≥ 4 mm, of which 36% had occult LNM (pN+). Patients in the watchful waiting group (48%) developed a regional recurrence in 5.2% for DOI < 4 mm and 24.1% for DOI ≥ 4 mm. For DOI ≥ 4 mm, regional recurrence free survival was higher for patients who were treated with END compared to watchful waiting (p = 0.002). A Receiver-Operator-Curve -analysis showed that a DOI cut-off value of 4.0 mm was the optimal threshold for the prediction of occult LNM (95.1% sensitivity, 52.9% specificity)., Conclusion: A DOI of ≥ 4 mm is an accurate cut-off value for performing an END in early stage OCSCC. END results in higher survival rates and lower regional recurrence rates in patients with DOI ≥ 4 mm., (Copyright © 2020. Published by Elsevier Ltd.)

Background: Our aim was to review our management of inverted papilloma (IP), perform a recurrence analysis, and review the literature., Methods: A retrospective analysis of 247 patients treated for an IP. Patients were grouped according to surgical approach, tumor presentation (primary, residual and recurrence) and Krouse-stage., Results: Recurrence was observed in 20.3%, 28.6% and 35.1% (p = 0.017) of the patients who underwent endoscopic, external and combined surgery, respectively. Recurrences occurred more often in residual than primary IP (36.9% vs. 22.3%, p = 0.021). Primary endoscopic surgery had a recurrence rate of 12.5%, which was comparable to the recent literature (11.2%, 161/1433)., Conclusions: The relatively high number of recurrences in this cohort is explained by the long follow-up and previous (incomplete) surgery in 61.5% of the cases. The inferior outcome of residual IP underscores the importance of having a low threshold for preoperative biopsy in unilateral and atypical sinonasal disease.

Oncological applications of Raman spectroscopy have been contemplated, pursued, and developed at academic level for at least 25 years. Published studies aim to detect pre-malignant lesions, detect cancer in less invasive stages, reduce the number of unnecessary biopsies and guide surgery towards the complete removal of the tumour with adequate tumour resection margins. This review summarizes actual clinical needs in oncology that can be addressed by spontaneous Raman spectroscopy and it provides an overview over the results that have been published between 2007 and 2017. An analysis is made of the current status of translation of these results into clinical practice. Despite many promising results, most of the applications addressed in scientific studies are still far from clinical adoption and commercialization. The main hurdles are identified, which need to be overcome to ensure that in the near future we will see the first Raman spectroscopy-based solutions being used in routine oncologic diagnostic and surgical procedures.

Objectives: Sinonasal inverted papilloma (IP) has several unfavourable characteristics and therefore requires careful monitoring. The goal of this study was to identify whether serum squamous cell carcinoma antigen (SCCa) could predict IP recurrence., Design: A retrospective cohort study., Setting: Department of otolaryngology/head and neck surgery, Erasmus Medical Centre, Rotterdam, the Netherlands., Participants: One hundred and thirty patients with IP treated at our centre with SCCa measurements available were included., Main Outcome Measurements: Follow-up of patients with IP since 2005, recurrence was defined as new disease within primary localisation at least 3 months after adequate surgical removal. We analysed the association between IP recurrence and serum SCCa values measured preoperatively, postoperatively and during follow-up., Results: Preoperative SCCa values or values measured during follow-up were not associated with risk of recurrence. Postoperative SCCa was positively associated with the risk of recurrence (P < 0.001). Postoperative SCCa had a good discriminative ability for the identification of recurrence with an area under the curve of 80.9%., Conclusion: Postoperative SCCa is strongly associated with risk of recurrence. This might help the surgeon in the postoperative setting by identifying high-risk patients and planning follow-up strategy tailored to the individual patient., (© 2016 John Wiley & Sons Ltd.)

Different surgical techniques exist for the treatment of Zenker's diverticulum (ZD), of which minimally invasive techniques have become the standard. We reviewed our experience with management and treatment of ZD and sought to determine what type of treatment is most effective and efficient. We selected patients who underwent treatment for ZD between January 2004 and January 2014 at our tertiary referral center. All procedures were performed by ENT surgeons. The medical records were reviewed for pre- and intraoperative characteristics and follow-up. Of our 94 patients (58 male, 36 female), 75 underwent endoscopic cricopharyngeal myotomy (42 stapler, 33 laser) and 6 received treatment via transcervical approach. 13 interventions were aborted. Mean operating time was 49.0 min for stapler, 68.3 for laser and 124.0 for the transcervical approach. Its respective median post-operative admission durations were 2.0, 3.0 and 3.0 days. After the first treatment, of the 75 endoscopic procedures, 45 patients (23 stapler, 22 laser) had complete symptom resolution. In the transcervical group 4 (67 %) patients were symptom free and one patient died of complications. In the endoscopically treated patients, ten complications occurred, of which 8 G1 and 2 G2 (Clavien Dindo classification). In the transcervical group 2 complications occurred, 1 G3b and 1 G5. Both endoscopic techniques provide efficient management of Zenker's diverticulum with the stapler-assisted modality providing a shorter surgery duration and hospital admission. Although there is no significant difference in terms of complications or recurrence rates for both endoscopic techniques, it seems that stapler patients are at higher risk of having a re-intervention and of having more severe complications., Competing Interests: The authors declare that they have no conflict of interest. The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper. Ethical standards All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. For this type of study formal consent is not required.

Introduction: The treatment of choice for early glottic cancer is still being debated; ultimately it relies on the functional outcome. This paper reports on a novel sparing 4D conformal technique for single vocal cord irradiation (SVCI)., Material and Methods: The records of 164 T1a patients with SCC of the vocal cord, irradiated in the Erasmus MC between 2000 and 2008, were analyzed for local control and overall survival. The quality of life was determined by EORTC H&N35 questionnaires. Also the VHI (voice handicap index), and the TSH (thyroid stimulating hormone) blood levels, were established. On-line image guided SVCI, using cone beam CT or stereotactic radiation therapy (SRT) techniques, were developed., Results: A LC rate at five-years of 93% and a VHI of 12.7 (0-63) was determined. It appeared feasible to irradiate one vocal cord within 1-2mm accuracy. This way sparing of the contralateral (CL) vocal cord and CL normal tissues, could be achieved., Conclusions: Given the accuracy (1-2mm) and small volume disease (CTV limited to one vocal cord), for the use of stereotactic RT techniques SVCI with large fraction sizes is currently being investigated in clinic. It is argued that hypofractionated SVCI can be a competitive alternative to laser surgery., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)