Computational Investigation of Precursor Blocking during Area-Selective Atomic Layer Deposition Using Aniline as a Small-Molecule Inhibitor.

Area-selective atomic layer deposition using small-molecule inhibitors (SMIs) involves vapor-phase dosing of inhibitor molecules, resulting in an industry-compatible approach. However, the identification of suitable SMIs that yield a high selectivity remains a challenging task. Recently, aniline (C6H5NH2) was shown to be an effective SMI during the area-selective deposition (ASD) of TiN, giving 6 nm of selective growth on SiO2 in the presence of Ru and Co non-growth areas. In this work, using density functional theory (DFT) and random sequential adsorption (RSA) simulations, we investigated how aniline can effectively block precursor adsorption on specific areas. Our DFT calculations confirmed that aniline selectively adsorbs on Ru and Co non-growth areas, whereas its adsorption on the SiO2 growth area is limited to physisorption. DFT reveals two stable adsorption configurations of aniline on the metal surfaces. Further calculations on the aniline-functionalized surfaces show that the aniline inhibitor significantly reduces the interaction of Ti precursor, tetrakis(dimethylamino)titanium, with the non-growth area. In addition, RSA simulations showed that the co-presence of two stable adsorption configurations allows for a high surface inhibitor coverage on both Co and Ru surfaces. As the surface saturates, there is a transition from the thermodynamically most favorable adsorption configuration to the sterically most favorable adsorption configuration, which results in a sufficiently dense inhibition layer, such that an incoming precursor molecule cannot fit in between the adsorbed precursor molecules. We also found that, as a result of the catalytic activity of the metallic non-growth area, further reactions of inhibitor molecules, such as hydrogenolysis, can play a role in precursor blocking.

Care Pathway Analysis to Inform the Earliest Stages of Technology Development: Scoping Oncological Indications in Need of Innovation.

OBJECTIVES: Identifying unmet needs for innovative solutions across disease contexts is challenging but important for directing funding and research efforts and informing early-stage decisions during the innovation process. Our aim was to study the merits of care pathway analysis to scope disease contexts and guide the development of innovative devices. We used oncologic surgery as a case study, for which many intraoperative imaging techniques are under development. METHODS: Care pathway analysis is a mapping process, which produces graphical maps of clinical pathways using important outcomes and subsequent consequences. We performed care pathway analyses for glioblastoma, breast, bladder, prostate, renal, pancreatic, and oral cavity cancer. Differences between a "perfect" care pathway and the current care pathway in terms of percentage of inadequate margins, associated recurrences, quality of life, and 5-year overall survival were calculated to determine unmet needs. Data from The Netherlands Cancer Registry and literature were used. RESULTS: Care pathway analysis showed that highest percentages of inadequate margins were found in oral cavity cancer (72.5%), glioblastoma (48.7%), and pancreatic cancer (43.9%). Inadequate margins showed the strongest increase in recurrences in cancer of oral cavity, and bladder (absolute increases of 43.5% and 41.2%, respectively). Impact on survival was largest for bladder and oral cavity cancer with positive margins. CONCLUSIONS: Care pathway analysis provides overviews of current clinical paths in multiple indications. Disease contexts can be compared via effectiveness gaps that show the potential need for innovative solutions. This information can be used as basis for stakeholder involvement processes to prioritize care pathways in need of innovation.

[Personalised follow-ups for patients curatively treated for squamous cell carcinoma in the oral cavity]. / Gepersonaliseerde nacontrole bij patiënten die curatief zijn behandeld voor een plaveiselcelcarcinoom in de mondholte.

As a result of an increase in the incidence of oral cancer and improving survival rates, the number of patients needing follow-up care will increase in the Netherlands. At present, these patients enroll in a 5-year follow-up programme aiming for early detection of recurrences or second primary tumors and improving their prognosis of life expectancy, among other things. Recurrences mostly occur in the first 2 years after treatment, whereas patients have a lifelong elevated risk of second primary tumors. 75% of second primary tumors occur outside the oral cavity and over 50% outside the head and neck area, places not routinely checked. There is no convincing evidence this 5-year follow-up programme yields survival benefits. It would therefore be better to limit follow-up care to 2 years and choose a subsequent follow-up programme better tailored to the individual patient's needs. This does not necessarily require the lead of a head and neck oncologist.

Imaging angiogenesis in patients with head and neck squamous cell carcinomas by [68Ga]Ga-DOTA-E-[c(RGDfK)]2 PET/CT.

PURPOSE: Angiogenesis plays an important role in the growth and metastatic spread of solid tumours and is characterised by the expression of integrins on the cell surface of endothelial cells. Radiolabelled RGD peptides specifically target angiogenesis-related αvß3 integrins, expressed on the activated endothelial cells of sprouting blood vessels. Here, we validated the feasibility of 68Ga[Ga]-DOTA-E-[c(RGDfK)]2 (68Ga-RGD) PET/CT to visualise angiogenesis in patients with oral squamous cell carcinoma (OSCC). METHODS: Ten patients with OSCC and scheduled for surgical resection including elective neck dissection received an intravenously administration of 68Ga-RGD (42 ± 8 µg; 214 ± 9 MBq). All patients subsequently underwent dynamic (n = 5) or static PET/CT imaging (n = 5) for 60 min or for 4 min/bed position at 30, 60 and 90 min after injection, respectively. Quantitative tracer uptake in tumour lesions was expressed as standardised uptake values (SUV). Additionally, tumour tissue was immunohistochemically stained for αvß3 integrin to assess the expression pattern. RESULTS: 68Ga-RGD tumour accumulation was observed in all patients. At 60 min post injection, tumour SUVmax ranged between 4.0 and 12.7. Tracer accumulation in tumour tissue plateaued at 10 min after injection. Uptake in background tissue did not change over time, resulting in tumour-to-muscle tissue of 6.4 ± 0.7 at 60 min post injection. CONCLUSIONS: 68Ga-RGD PET/CT of αvß3 integrin expression in OSCC patients is feasible with adequate tumour-to-background ratios. It will provide more insight in angiogenesis as a hallmark of the head and neck squamous cell carcinomas' tumour microenvironment. TRIAL REGISTRATION: https://eudract.ema.europa.eu no. 2015-000917-31.

[Factors contributing to a delay in the diagnostic process in oral cancer]. / Factoren die bijdragen aan het delay in het diagnostisch proces van een mondholtetumor.

In patients with a new squamous cell carcinoma in the oral cavity, factors were investigated that determine the time interval between the occurrence of the first symptoms, the diagnosis and the start of treatment. Status research was conducted on 87 patients who were diagnosed in 2017 at the department of Oral and Maxillofacial Surgery at the Radboud university medical centre (Radboudumc), Nijmegen, the Netherlands. Patients were asked about the length of time between the appearance of the first symptoms and their visit to the dentist or general practioner. Especially patients who were not registered with a dentist waited on average 2 months longer, the most important reasons being that they thought it would solve itself and treatment anxiety. It was concluded that in the case of a squamous cell carcinoma, patients who are not registered with a dentist, are more often toothless and present later with a larger tumour than patients registered with a dentist. Training on recognising the first symptoms of squamous cell carcinomas in the oral cavity should be intensified among dentists and also general practitioners, dental hygienists and dental prosthetic technicians.

Needs and preferences of patients with head and neck cancer in integrated care.

OBJECTIVES: Incorporation of patients' perspectives in daily practice is necessary to adapt care to users' needs. However, information on patients' needs and preferences for integrated care is lacking. The aim was to explore these needs and preferences, taking patients with head and neck cancer (HNC) as example, to adapt current integrated care to be more patient-centred. DESIGN: Semi-structured interviews were held with current and former patients and chairmen of patient associations. Relevant needs and preferences were identified and categorised using the eight-dimension Picker model of patient-centred care. SETTING: Integrated HNC in the Netherlands. PARTICIPANTS: Patients with HNC and chairmen of two Dutch HNC patient associations. MAIN OUTCOME MEASURES: Patients' needs and preferences of integrated HNC care categorised according the Picker model. RESULTS: A total of 34 themes of needs and preferences were identified, by 14 patients with HNC or their delegates, using the Picker dimensions. Themes often emerged were as follows: personalisation of health care regarding patient values; clear insight into the healthcare process at organisational level; use of personalised communication, education and information that meets patients' requirements; adequate involvement of allied health professionals for physical support; more attention to the impact of HNC and its treatment; adequate involvement of family and friends; adequate general practitioner involvement in the aftercare; and waiting time reduction. CONCLUSIONS: Monitoring the identified themes in integrated HNC care, fitting in the Picker model, will enable us to respond better to the needs and preferences of patients, and patient-centred care in oncological care can be enhanced.

Oral submucous fibrosis: An update on current theories of pathogenesis.

Over the last 40 years, many theories linking oral submucous fibrosis (OSMF) to various risk factors have been proposed. Spicy, pungent foods and irritants such as supari (areca nut), paan (betel leaves), tobacco (through chewing or smoking)-the common Asian habits of chewing the aforementioned agents-have all been incriminated as causative agents. Systemic factors such as nutritional deficiency, genetic predisposition and autoimmunity have also been proposed in the pathogenesis of OSMF. However, the precise aetiology of OSMF is still unknown, and no conclusive evidence has been found despite many extensive investigations on implicated factors. Most of the ideas proposed have been derived from the existing clinical and epidemiological data. We present a comprehensive review of the various theories regarding the pathogenesis of the condition, but have not concentrated on malignant transformation in this article.

Current protocols in the management of oral submucous fibrosis: An update.

Oral submucous fibrosis (OSMF) is a debilitating condition of oral cavity which has significant potential for malignant transformation. In spite of over 20 years of research, the pathogenesis of the condition is still obscure and no single management modality is effective. Many OSMF treatment protocols have been proposed to alleviate the signs and symptoms of the disorder and there is overwhelming evidence that as areca nut is primary cause, stopping its use may have a considerable effect on symptoms rather than reversing pre-existing fibrosis. We present a review of the current protocols for managing OSMF.

Oral submucous fibrosis: An update on pathophysiology of malignant transformation.

Oral submucous fibrosis (OSMF) is a potentially malignant condition associated with areca nut chewing. Formerly confined to the Indian subcontinent, it is now often seen in Asian populations of the United Kingdom, USA and other developed countries, and is therefore a serious problem for global health. What makes it more sinister is the malignant transformation rate, which has been reported to be around 7.6% over a 17-year period. In this concise article, we review the current trends in the pathophysiology of malignant transformation of OSMF.

Quality of life after different procedures for regional control in oral cancer patients: cross-sectional survey.

OBJECTIVES: To examine health utilities in patients with cT1-2 oral cavity squamous cell carcinoma following different diagnostic and treatment modalities for the neck and to investigate the relation between shoulder morbidity and health utility. DESIGN: Cross-sectional survey. SETTING: Two Dutch hospitals. PARTICIPANTS: Four subgroups of patients with oral cavity cancer who underwent watchful waiting, sentinel lymph node biopsy, elective supraomohyoid neck dissection or therapeutic modified radical neck dissection. MAIN OUTCOME MEASURES: Patients received the EuroQol-5D-3L questionnaire and the shoulder disability questionnaire. Mean health utility, visual analogue scale and shoulder disability scores were calculated. RESULTS: A total of 181 patients (62%) returned the questionnaires. Mean health utilities, adjusted for age, gender and time since treatment were 0.804, 0.863, 0.834 and 0.794 for the watchful waiting, sentinel lymph node biopsy, supraomohyoid neck dissection and modified radical neck dissection subgroups, respectively. Mean shoulder disability scores (higher score means more shoulder complaints) for these subgroups were 8.64, 10.57, 18.92 and 33.66. Patients with shoulder complaints had a mean utility of 0.78 while patients without shoulder complaints had a mean utility of 0.90. CONCLUSIONS: This study shows that more invasive procedures appear to result in lower health utility. The high health utility for patients after sentinel lymph node biopsy supports a role for this procedure in patients with oral cancer.

[Gout in the temporomandibular joint]. / Jicht in het temporomandibulaire gewricht.

A 76-year-old woman, with a medical history of diabetes mellitus and hypertension, presented herself to an oral and maxillofacial surgeon with a sudden pre-auricular swelling of the right temporomandibular joint. As a result of the atypical clinical appearance and signs of local destruction in the initial panoramic x-ray, a malign process was first eliminated from consideration. With the aid of extensive diagnostics and an open biopsy, the diagnosis of gout was established.

The Consequences of Random Sequential Adsorption for the Precursor Packing and Growth-Per-Cycle of Atomic Layer Deposition Processes.

Atomic layer deposition (ALD) processes are known to deposit submonolayers of material per cycle, primarily attributed to steric hindrance and a limited number of surface sites. However, an often-overlooked factor is the random sequential adsorption (RSA) mechanism, where precursor molecules arrive one-by-one and adsorb at random surface sites. Consequently, the saturation coverage of precursors significantly deviates from ideal closed packing. In this study, we investigated the influence of RSA on precursor adsorption saturation and, consequently, on the growth per cycle (GPC) of the ALD processes. Our simulations revealed that the RSA model leads to a 22% to 40% lower surface density compared to the reference case of ordered packing. Furthermore, based on the precursor shape and size, we estimated GPC values with an average accuracy of 0.05 Å relative to experimental literature data. This work shows the critical role of RSA in ALD, emphasizing the need to consider this mechanism for a more accurate process design and optimization.

[A diagnosed follicular cyst turned out to be a squamous cell carcinoma]. / Een gediagnosticeerde folliculaire cyste bleek een plaveiselcelcarcinoom.

A 50-year-old man had undergone a complicated removal of tooth 48 which initially seemed related to a follicular cyst. Subsequently, it turned out that a squamous cell carcinoma had probably developed from the follicular cyst. The patient underwent excision of the tumour, hemimandibulectomy, a neck dissection, and reconstruction of the mandibula using a metal plate, followed by postoperative local radiotherapy. This type of development of a squamous cell carcinoma presents very rarely. From the literature, it can be concluded that the prognosis is unfavourable and that the tumour tends to grow aggressively. In case of abnormal wound healing after the removal of a tooth (with a follicular cyst), it is recommended to examine representative tissue histologically.

Feasibility of non-contrast-enhanced magnetic resonance angiography for imaging upper extremity vasculature prior to vascular access creation.

OBJECTIVES: Preoperative mapping of arterial and venous anatomy helps to prevent postoperative complications after vascular access creation. The use of gadolinium in contrast-enhanced (CE) magnetic resonance angiography (MRA) has been linked to nephrogenic systemic fibrosis in patients with end-stage renal disease (ESRD). The purpose of this study was to evaluate non-contrast-enhanced (NCE) MRA for assessment of upper extremity and central vasculature and to compare it with CE-MRA. METHODS: NCE and CE-MRA images were acquired in 10 healthy volunteers and 15 patients with ESRD. In each data set, two observers analysed 11 arterial and 16 venous segments with regard to image quality (0-4), presence of artefacts (0-2) and vessel-to-background ratio. RESULTS: More arterial segments were depicted using CE-MRA compared to NCE-MRA (99% vs. 96%, p = 0.001) with mean image quality of 3.80 vs. 2.68, (p < 0.001) and mean vessel-to-background ratio of 6.47 vs. 4.14 (p < 0.001). Ninety-one percent of the venous segments were portrayed using NCE-MRA vs. 80% using CE-MRA (p < 0.001). Mean image quality and vessel-to-background ratio were 2.41 vs. 2.21 (p = 0.140) and 5.13 vs. 3.88 (p < 0.001), respectively. CONCLUSIONS: Although arterial image quality and vessel-to-background ratios were lower, NCE-MRA is considered a feasible alternative to CE-MRA in patients with ESRD who need imaging of the upper extremity and central vasculature prior to dialysis access creation.

[A peripheral osteoma]. / Een perifeer osteoom.

A 43-year-old man appeared with a painless, asymptomatic swelling on the left side of his neck, which had existed for years and had slowly been progressing. After surgical removal, it became clear that it had to do with a peripheral osteoma. This is a benign lesion with a low incidence. Generally, complete surgical removal leads to cure, although recurrence is possible. A peripheral osteoma is mostly located in the mandible, although peripheral osteomata in the frontal or maxillary sinus have been described. The aetiology is unknown. Trauma in the patient's history has been described on occasion. The presence of multiple osteomata in the jawbones is characteristic of Gardner's syndrome.

[Sclerosis of lymfangiomas in the head and neck area: evaluation with the use of stereophotogrammetry]. / Sclerosering van lymfangiomen in her hoofd-halsgebied: evaluatie door middel van stereofotogrammetrie.

Lymangiomas are congenital malformations of the lymphatic system. They can appear at any age and in any part of the body. In the head and neck area lymangiomas can give rise to functional as well as esthetic problems. Therapy consist of sclerosis, possibly followed by surgical excision. Stereophotogrammetry is a relatively new technique which, by means of superimposition of pre- and postoperative images, provides the possibility to quantify treatment results. In this paper 3 patients who underwent treatment of a lymphatic malformation and in whom treatment results were measured with stereophotogrammetry are discussed. The conclusion can be drawn that stereophotogrammetry is a promising technique for evaluation of treatment results of superficially localised lymphatic malformations that displace the skin in the head and neck area.

Does hyperbaric oxygen therapy play a role in the management of osteoradionecrosis? A survey of Dutch oral and maxillofacial surgeons.

For decades, hyperbaric oxygen (HBO) has often been part of the treatment of osteoradionecrosis (ORN), despite controversy in the literature about its efficacy. An online survey was conducted to investigate the use of HBO in the treatment of ORN by Dutch oral and maxillofacial surgeons and to assess their perception of its efficacy. Of the 53 Dutch oral and maxillofacial surgery units contacted, 49 (92%) replied. Thirty-five were not head and neck cancer (HNC) units or preferred partner (PP-HNC) units recognized by the Dutch Head and Neck Association. All HNC and PP-HNC units (group 1) treated ORN patients, compared to only 12 (34%) of the non-HNC units (group 2). The average number of ORN patients seen and treated was higher in group 1. The units in group 1 more often referred patients for HBO therapy (HBOT) than those in group 2 (93% vs 84%). The efficacy of HBOT in curing ORN, rated on a scale of 1 to 5 points, was 3.7 in group 1 and 3.2 in group 2. This survey shows a trend towards centralization of ORN care to more experienced units. These units tend to use HBOT in curing ORN.

Immediate implant placement in edentulous oral cancer patients: a long-term retrospective analysis of 207 patients.

Although the functional benefits of implants in the rehabilitation of edentulous cancer patients are well-known, most studies report on postponed implant placement. The outcome of immediate implant placement regarding successful rehabilitation, implant loading and survival is unclear. Two hundred and seven edentulous oral cancer patients that received implants during ablative surgery at the Radboud University Medical Centre between 2000 and 2011 were included. Data regarding the oncological treatment, implant placement, follow-up and prosthodontic rehabilitation were recorded retrospectively with a follow-up period of 5-17 years. Functioning implant-retained dentures were made in 73.9% of the patients. Of the surviving patients, 81.9% had functioning dentures after 2 years and 86.3% after 10 years. Patients with ASA score 1 and younger patients were rehabilitated more frequently. The median time of functioning denture placement was 336 days after surgery, with a negative influence of postoperative radiotherapy. Implant survival was 90.7%, and was lower when the implant was placed in a jaw involved in the tumour. Immediate implant placement during oral cancer surgery led to a high number of edentulous patients rehabilitated with implant-retained dentures, which are placed at an early time.

[Painless swelling proved to be a central giant cell granuloma]. / Pijnloze zwelling bleek een centrale reuscellaesie.

A 32-year-old female patient was referred to an oral and maxillofacial surgeon with an asymptomatic swelling in the left mandibular premolar region. After extraction of these premolars and enucleation of the lesion histopathological examination confirmed the presence of a giant cell granuloma. This is a benign lesion and enucleation generally results in a permanent cure and is only recurrent in a few cases. Approximately 1 year after treatment, the patient was still free of recurrence and together with a prosthodontist, the appropriate rehabilitation of the resulting defect will be sought.