The Summer School Oncology Groningen: Improving a Successful International Course by Refining the Old, Maintaining What's Good.

For more than two decades, the International Summer School Oncology for Medical Students (ISOMS) has organized a biennial 2-week international summer school program in Groningen, the Netherlands. The summer school aims to increase knowledge about general cancer care, reduce fear of talking to cancer patients, and expose students to cancer-related problems. After 22 years, there was a need to improve the summer school format, the application procedure, and the intensity of the course. Here, we describe and evaluate these and additional changes that were made to the program. Several changes were made to the summer school format. The course was shortened from 10 days to a more intensive 7 days. The scientific program was integrated with the clinical program and students were taught scientific writing and presentation skills. The application process involved a personal video pitch. Importantly, the new summer school format was organized by a committee in which medical students had the lead. To evaluate the changes to the summer school, we conducted knowledge tests and regularly obtained feedback. There was a high overall student satisfaction, with a median score of a 9 out of 10. Students appreciated the interactive sessions and practicals and the scientific program, and were satisfied with the course level. All students had improved test scores. Improvement points highlighted the need for a less packed schedule and more lectures on basic oncology principles, or were related to specific lectures. The student-led innovation and adaptation of the ISOMS has been successful.

Evaluation of change in dietitians' perceived comprehensibility and difficulty of the Patient-Generated Subjective Global Assessment (PG-SGA) after a single training in the use of the instrument.

BACKGROUND: The Patient-Generated Subjective Global Assessment (PG-SGA) is an instrument used to assess malnutrition and its risk factors. Some items of the PG-SGA may be perceived as hard to comprehend or as difficult by healthcare professionals. The present study aimed to determine whether and how dietitians' perceptions of comprehensibility and difficulty of the PG-SGA change after a single training in PG-SGA use. METHODS: In this prospective evaluation study, Dutch PG-SGA-naïve dietitians completed a questionnaire regarding perceived comprehensibility and difficulty of the PG-SGA before (T0) and after (T1) receiving a single training in the use of the instrument. Perceived comprehensibility and difficulty were operationalised by calculating item and scale indices for comprehensibility (I-CI, S-CI) and difficulty (I-DI, S-DI) at T0 and T1. An item index of 0.78 was considered acceptable, a scale index of 0.80 was considered acceptable and a scale index of 0.90 was considered excellent. RESULTS: A total of 35 participants completed the questionnaire both at T0 and T1. All item indices related to comprehensibility and difficulty improved, although I-DI for the items regarding food intake and physical examination remained below 0.78. Scale indices for difficulty and comprehensibility of the PG-SGA changed significantly (P < 0.001) from not acceptable at T0 (S-CI = 0.69; S-DI = 0.57) to excellent for comprehensibility (S-CI = 0.95) and acceptable for difficulty (S-DI = 0.86) at T1. CONCLUSIONS: The findings of the present study suggest that significant improvement in PG-SGA-naïve dietitians' perception of comprehensibility and difficulty of the PG-SGA can be achieved quickly by providing a 1 day of training in the use of the PG-SGA.

High sensitivity and negative predictive value of sentinel lymph node biopsy in a retrospective early stage oral cavity cancer cohort in the Northern Netherlands.

OBJECTIVES: In cT1-2N0, oral squamous cell carcinoma (OSCC) occult metastases are detected in 23%-37% of cases. Sentinel lymph node biopsy (SLNB) was introduced in head and neck cancer as a minimally invasive alternative for an elective neck dissection in neck staging. Meta-analyses of SLNB accuracy show heterogeneity in the existing studies for reference standards, imaging techniques and pathological examination. The aim of this study was to assess the sensitivity and negative predictive value (NPV) of the SLNB in detecting occult metastases in cT1-2N0 OSCC in a well-defined cohort. DESIGN: Retrospective study. The SLNB procedure consisted of lymphoscintigraphy, SPECT/CT-scanning and gamma probe detection. Routine follow-up was the reference standard for the SLNB negative neck. Histopathological examination of sentinel lymph nodes (SLN) consisted of step serial sectioning, haematoxylin-eosin and cytokeratin AE1/3 staining. SETTING: Two comprehensive oncology centres. PARTICIPANTS: A total of 91 consecutive patients with primary cT1-2N0 OSCC treated by primary resection and neck staging by SLNB procedure between 2008 and 2016. MAIN OUTCOME MEASURES: Sensitivity and negative predictive value. RESULTS: In all cases, SLNs were harvested. A total of 25 (27%) patients had tumour-positive SLNs. The median follow-up was 32 months (range 2-104). Four patients were diagnosed with an isolated regional recurrence in the SLNB negative neck side resulting in an 85% sensitivity and a 94% NPV. CONCLUSION: In our cohort, the SLNB detected occult metastases in early OSCC with 85% sensitivity and 94% NPV. This supports that SLNB is a reliable procedure for surgical staging of the neck in case of oral cT1-2N0 SCC.

Clinical outcome of salvage neck dissections in head and neck cancer in relation to initial treatment, extent of surgery and patient factors.

OBJECTIVE: Salvage surgery has a higher complication rate compared to primary surgical treatment. We evaluated clinical outcome of salvage neck dissections in relation to initial treatment modality, extent of surgery and patient-related factors. DESIGN: Single institution consecutive case series. SETTING: Tertiary Head and Neck Cancer Centre. PARTICIPANTS: In all, 87 patients with head and neck squamous cell carcinoma, who underwent salvage neck dissection after initial radiotherapy (n = 30), radiotherapy with carboplatin/5-fluorouracil (n = 43) or radiotherapy with cetuximab (n = 14). MAIN OUTCOME MEASURES: Incidence of complications, disease-specific survival. RESULTS: Complications occurred in 28% of the patients. Multivariate analysis identified extent of neck dissection as the only independent predictor of surgical complications (P = 0.010). Surgical complication rate was 16% after radiotherapy with systemic treatment, and 47% after radiotherapy alone (P = 0.171). The 5-year disease-specific survival was 55%, independent of complications, initial treatment, extent of surgery and patient-related factors. CONCLUSION: The only predictor for surgical complications was extent of surgery. Survival was not influenced by complications.

Detection of HPV-associated oropharyngeal tumours in a 16-year cohort: more than meets the eye.

BACKGROUND: Accurate assessment of the prevalence of the human papilloma virus (HPV) in oropharyngeal tumours (OpSCC) is important because HPV-positive OpSCC are consistently associated with an improved overall survival. Recently, an algorithm has become available that reliably detects clinically relevant HPV in tumour tissue, however, no complete cohorts have been tested. The aim was to determine the prevalence of active high-risk HPV infection in a complete cohort of OpSCC collected over a 16-year period. METHODS: Using a triple algorithm of p16 immunohistochemistry, HPV-BRISH and HPV-PCR, we assessed the prevalence of active HPV infection in all OpSCC diagnosed in our hospital from 1997 to 2012 (n=193) and a random selection of 200 oral tumours (OSCC). RESULTS: Forty-seven OpSCC (24%) were HPVGP PCR-positive; 42 cases were HPV16+, 1 HPV18+, 3 HPV33+ and 1 HPV35+. Brightfield in situ hybridisation did not identify additional HPV-positive cases. Human papilloma virus-associated tumour proportion increased from 13% (1997-2004) to 30% (2005-2012). Human papilloma virus-positivity was an independent predictor for longer disease-specific survival (HR=0.22; 95%CI:0.10-0.47). Only one OSCC was HPV+. CONCLUSIONS: In our cohort, the incidence of HPV-associated OpSCC is low but increasing rapidly. The strict detection algorithm, analysis of disease-specific survival and the complete cohort, including palliatively treated patients, may influence the reported prevalence and prognostic value of HPV in OpSCC.

Trismus in patients with head and neck cancer: etiopathogenesis, diagnosis and management.

BACKGROUND: Trismus indicates severely restricted mouth opening of any aetiology. A mouth opening of 35 mm or less should be regarded as trismus. Aim of this study was to review the etiopathogenesis, incidence, treatment and prevention of trismus in patients with head and neck cancer. OBJECTIVE OF REVIEW: Trismus is frequently seen in patients suffering from malignant tumours of the head and neck. The reported prevalence of trismus in those patients varies considerably in the literature and ranges from 0 to 100% depending on the tumour site and extension. Trismus may worsen or remain the same over time, or the symptoms may reduce, even in the absence of treatment. When a patient presents with trismus after tumour treatment, it is important to determine whether the trismus is the result of the treatment, or is the first sign of a recurrence. Restricted mouth opening may impede inspection of the oral cavity as needed for dental care, and particularly for oncologic follow-up. CONCLUSIONS: Mouth opening after radiotherapy (RT) decreases on average by approximately 20% compared to mouth opening prior to RT. The prevalence of trismus increases with increasing doses of RT to mastication structures. The use of intensity-modulated RT seems to lower the percentage and severity of RT-induced trismus. Treatment of trismus can be conservative (with either medical or physical therapy) or surgical. Exercise therapy is the mainstay of treatment and exercise should start as soon as possible after treatment. The prevention of trismus, rather than its treatment, is the most important objective.

FADD expression is associated with regional and distant metastasis in squamous cell carcinoma of the head and neck.

AIMS: The Fas-associated death domain gene (FADD) is often overexpressed in squamous cell carcinoma of the head and neck (HNSCC), and is considered to be a driver gene in amplification of the chromosomal 11q13.3 region. Amplification of 11q13.3 is associated with increased metastasis in HNSCC and breast cancer. The aim of this study was to investigate the association between FADD protein expression in advanced-stage HNSCC and clinicopathological features and outcome. METHODS AND RESULTS: Tumour tissues of 177 HNSCC patients uniformly treated with primary surgery and postoperative radiotherapy were collected. FADD expression was assessed on pretreatment tumour biopsies using immunohistochemistry. High FADD expression was detected in 44% of the HNSCC patients. High expression was associated with an increased rate of lymph node metastasis (P = 0.001) and with a shorter distant metastasis-free interval (DMFI) (HR 2.6, 95% CI 1.0-6.7, P = 0.046) when lymph node metastases were present. CONCLUSIONS: Our data show that an increase in FADD expression is associated with a higher incidence of lymph node metastasis at presentation, and with shorter DMFI when lymph node metastases are present. High FADD expression in the primary tumour could be a useful marker to select patients for systemic treatment strategies that reduce the risk of distant metastases.

[Three dimensional technology and reconstructions of large defects of the jaw]. / Driedimensionale technologie en reconstructies van grote kaakdefecten.

3D technology is increasingly being applied in dentistry and in oral and maxillofacial surgery. An important field of application is reconstructive surgery, especially in the reconstruction of large defects ofthe jaw. In such cases of reconstruction, the goal is the restoration of both the continuity of the defective area and its function. For the functional restoration implant supported dental structures are often employed. In such cases, CAD/CAM superstructures, 3D printed drill and saw templates, anatomical models, wafers and surgical outcome models are used. The combination of the digital planning and the digital fabrication ofsuperstructures and surgical aids offers many preoperative advantages. The use of saw, drill and positioning templates provides for accurate segmentation and implant positioning, by means of which the reconstruction can be carried out in a predictable way.

[Dissertations 25 years after date 29. CO2 laser surgery of leukoplakia of the oral mucosa]. / Proefschriften 25 jaar na dato 29. CO2-laser chirurgie van leukoplakie van het mondslijmvlies.

With a CO2 laser superficial lesions of the oral mucosa can be removed by evaporation. During CO2 laser evaporation there is minimal damage to the surrounding tissue, resulting in minimal scarring after healing. Therefore the CO2 laser seems to be a modality which is appropriate for the treatment of leukoplakia of the oral mucosa. In 1985, the effect of CO2 laser light on mucosa and the healing after CO2 laser evaporation was studied. In addition, clinical research was carried out concerning the effectiveness of CO2 laser evaporation in the treatment of 103 cases of leukoplakia of the oral mucosa The cure-rate was 91% and no malignant degenerations were seen in the treated area. The group was expanded (282) and evaluated again, with a cure-rate of 90%. In 1% of the cases, malignant degenerations were seen. CO2 laser evaporation seems the modality of choice for the treatment of leukoplakia of the oral mucosa.

The phosphatase and tensin homologue deleted on chromosome 10 mediates radiosensitivity in head and neck cancer.

BACKGROUND: For locally advanced squamous cell carcinoma of the head and neck (HNSCC), the recurrence rate after surgery and postoperative radiotherapy is between 20 and 40%, and the 5-year overall survival rate is approximately 50%. Presently, no markers exist to accurately predict treatment outcome. Expression of proteins in the human epidermal growth factor receptor (EGFR) pathway has been reported as a prognostic marker in several types of cancer. METHODS: The aim of this study was to investigate the prognostic value of proteins in the EGFR pathway in HNSCC. For this purpose, we collected surgically resected tissue of 140 locally advanced head and neck cancer patients, all treated with surgery and postoperative radiotherapy. RESULTS: In a multivariate analysis, expression of the phosphatase and tensin homologue deleted on chromosome 10 (PTEN) was significantly related to worse locoregional control (LRC; HR: 2.2, 95% CI: 1.1-4.6; P=0.03), independent of lymph node metastases (HR: 5.6, 95% CI: 1.2-27.4; P=0.03) and extranodal spread (HR: 2.7; 95% CI: 1.2-6.5; P=0.02). In vitro clonogenic radiosensitivity assays confirmed that overexpression of PTEN resulted in increased radioresistance. CONCLUSION: Our study is the first report showing that expression of PTEN mediates radiosensitivity in vitro and that increased expression in advanced HNSCC predicts worse LRC.

Conflicts and conflict management in the collaboration between nurses and physicians - a qualitative study.

In health care, optimal collaboration between nurses and physicians is crucial in the quality of the care process – but not self-generating. Little is known about how health-care professionals cope with conflicts within their collaboration. This qualitative study investigates the way nurses and physicians cope with conflict and clarifies the determinants of conflict management styles. All respondents formulate clear expectations which in their opinion are essential to collaboration. When collaboration leads to disagreement, physicians and nurses choose between ignoring the conflict or engaging in it. Choice is determined by five factors: the influence of oneself, the influence of the other, the nature of the conflict, the context of conflict, and personal motives.

[Cheek paresthesia by an osteosarcoma]. / Paresthesie van de wang door een osteosarcoom.

A 21-year-old woman was referred by the dental practitioner to an oral surgeon concerning a hard elastic swelling of the left cheek in combination with local paresthesia. Histopathologic and radiographic examination revealed an osteosarcoma in the left segment of the maxilla. Subsequently, the patient was referred to a medical centre for head and neck oncology. The treatment consisted of 3 courses neoadjuvant chemotherapy, followed by radical surgical resection of the tumor, and 3 courses adjuvant chemotherapy. One year after treatment, there was no sign of local tumor recurrence or metastases. An osteosarcoma is a malignant tumor of bone forming cells. About 10% of osteosarcomas are appearing in the head and neck region, primarily in the mandible and the maxilla. The treatment of choice is adequate surgical removal. Treatment with (neo)adjuvant chemotherapy seems to have additional benefit, but this needs further research.

Coexistence of malnutrition, frailty, physical frailty and disability in patients with COPD starting a pulmonary rehabilitation program.

BACKGROUND & AIMS: Malnutrition, frailty, physical frailty, and disability are common conditions in patients with chronic obstructive pulmonary disease (COPD). Insight in the coexistence and relations between these conditions may provide information on the nature of the relationship between malnutrition and frailty. Such information may help to identify required interventions to improve the patient's health status. We therefore aimed to explore whether malnutrition, frailty, physical frailty, and disability coexist in patients with COPD at the start of pulmonary rehabilitation. METHODS: For this cross-sectional study, from March 2015 to May 2017, patients with COPD were assessed at the start of a pulmonary rehabilitation program. Nutritional status was assessed with the Scored Patient-Generated Subjective Global Assessment (PG-SGA) based Pt-Global app. Frailty was assessed by the Evaluative Frailty Index for Physical activity (EFIP), physical frailty by Fried's criteria, and disability by the Dutch version of World Health Organization Disability Assessment Schedule 2.0 (WHODAS). These variables were dichotomized to determine coexistence of malnutrition, frailty, physical frailty, and disability. Associations between PG-SGA score and respectively EFIP score, Fried's criteria, and WHODAS score were analyzed by Pearson's correlation coefficient. Two tailed P-values were used, and significance was set at P < 0.05. RESULTS: Of the 57 participants included (age 61.2 ± 8.7 years), malnutrition and frailty coexisted in 40%. Malnutrition and physical frailty coexisted in 18%, and malnutrition and disability in 21%. EFIP score and PG-SGA score were significantly correlated (r = 0.43, P = 0.001), as well as Fried's criteria and PG-SGA score (r = 0.37, P = 0.005). CONCLUSIONS: In this population, malnutrition substantially (40%) coexists with frailty. Although the prevalence of each of the four conditions is quite high, the coexistence of all four conditions is limited (11%). The results of our study indicate that nutritional interventions should be delivered by health care professionals across multiple disciplines.

Variation in repeated mouth-opening measurements in head and neck cancer patients with and without trismus.

Trismus after head and neck cancer treatment may severely limit mandibular functioning. Interventions aimed at reducing trismus can only be evaluated when the amount of variation associated with these measurements is known. The aim of this study was to analyse the variation in mouth-opening measurements in patients treated for head and neck cancer, with and without trismus. Maximal mouth opening was measured in 120 patients in two sessions of three repeated measurements by one observer. To analyse the influence of interobserver variation on mouth-opening measurements a subgroup of 30 patients was measured by a second observer. The standard deviation of the six measurements per patient was used as the variation in measurements of maximal mouth opening. No significant difference was found in maximal mouth opening in patients with (n=33) or without (n=87) trismus. The interobserver intraclass correlation coefficient (ICC) was 0.98. Intraobserver ICC and intersession ICC reliabilities both were 0.99. The variation in the mean values of the three measurements was only slightly smaller than the variation of the single measurements. Variation in maximal mouth opening in patients with trismus does not differ from variation in maximal mouth opening in patients without trismus. Interobserver variation is limited.

Non-invasive measurement of the morphology and physiology of oral mucosa by use of optical spectroscopy.

Differential path-length spectroscopy (DPS) was used to non-invasively determine the superficial optical properties of oral mucosa in vivo. DPS yields information on physiological parameters such as the mucosal blood content, the microvascular blood oxygenation and the average micro-vessel diameter as well as on morphological parameters such as the scattering slope and scattering amplitude. DPS measurements were made on normal and cancerous oral mucosa using a novel fiber-optic probe, and were correlated to the histological outcome of punch biopsies taken from the same location. Our data shows that the mucosa of oral squamous cell carcinoma is characterised by a significant decrease in microvascular oxygenation and increase in mucosal blood content compared to normal oral mucosa as well as a significant decrease in scattering amplitude and increase in scattering slope.

Prosthodontic rehabilitation of oral function in head-neck cancer patients with dental implants placed simultaneously during ablative tumour surgery: an assessment of treatment outcomes and quality of life.

The aim of this prospective study was to assess treatment outcome and impact on quality of life of prosthodontic rehabilitation with implant-retained prostheses in head-neck cancer patients. Fifty patients were evaluated by standardized questionnaires and clinical assessment. All received the implants during ablative tumour surgery in native bone in the interforaminal area. About two-thirds of the patients (n=31) needed radiotherapy post-surgery. Both in irradiated and non-irradiated bone two implants were lost 18-24 months after installation. Peri-implant tissues had a healthy appearance. No cases of osteoradionecrosis occurred. In 15 patients no functional implant-retained lower dentures could be made for various reasons. The other 35 patients all functioned well, with an improvement in quality of life. Major improvement was observed in the non-irradiated patients. In the irradiated patients, less improvement in many functional items was observed, while items related to the oral sequelae of radiotherapy did not improve. Similar to the quality-of-life assessments, denture satisfaction was improved and tended to be higher in non-irradiated than irradiated patients. Implant-retained lower dentures can substantially improve the quality of life related to oral functioning and denture satisfaction in head-neck cancer patients. This effect is greater in non-irradiated than irradiated cancer patients.

CO2 laser evaporation of oral lichen planus.

Oral lichen planus is a relatively common disease of the oral mucosa. The buccal mucosa and lateral border of the tongue are mostly involved, although the condition can occur anywhere in the oral cavity. The erosive type in particular can cause spontaneous pain during eating. In the period from 1975 to 2003, a group of 21 patients with 39 lesions of oral lichen planus which caused pain, even after conservative therapy, were treated with CO2 laser evaporation. During a follow-up period of 1-18 years (mean 8 years) 21 patients were pain free (85%) and 6 patients (15%) experienced painful recurrence after treatment. After retreatment with CO2 laser evaporation there were no complaints of pain. Among the many treatments available, high-potency topical corticosteroids remain the most consistent and effective. In patients whose condition is unresponsive to topical corticosteroids, CO2 laser evaporation can cause long-term remission of symptoms, and may even be the treatment of first choice in patients suffering from painful oral lichen planus.

Secondary surgical management of osteoradionecrosis using three-dimensional isodose curve visualization: a report of three cases.

Osteoradionecrosis is defined as bone death secondary to radiotherapy. There is a relationship between the radiation dose received and the occurrence of osteoradionecrosis of the jaws, with the risk increasing above a dose of 60Gy. In cases of class III mandibular osteoradionecrosis, a segmental resection can be indicated. Current practice is to completely remove the affected bone up to the point where the bone looks healthy and is bleeding. Exact resection planning and the use of guided surgery based on imaging of the bone changes have not been reported so far. This article describes a method whereby the radiotherapy dose information is incorporated into the imaging of the affected bone in order to plan a three-dimensional (3D) virtual guided resection and reconstruction of the mandible in osteoradionecrosis. The method enables 3D visualization of each desired dose field in relation to the 3D model of the affected bone. Two types of application - for resection and reconstruction - are described.

Multi-modality 3D mandibular resection planning in head and neck cancer using CT and MRI data fusion: A clinical series.

OBJECTIVES: 3D virtual surgical planning (VSP) and guided surgery has been proven to be an effective tool for resection and reconstruction of the mandible. Currently, most widely used 3D VSP approaches to mandibular resection do not include detailed tumour information in the VSP. This manuscript presents a strategy where the aim was to incorporate tumour visualisation into the 3D virtual plan. Three-dimensional VSP of the mandibular resections was based on the fusion of CT and MRI data which was subsequently applied in clinical practice. METHODS: All patients diagnosed with oral squamous cell carcinoma between 2014 and 2017 at the University Medical Centre Groningen were included. The tumour was delineated on the MRI data, after which this dataset was fused with the CT bone data in order to construct a 3D bone and tumour model for virtual resection planning. Guided resections were performed and post-operative evaluation quantified the accuracy of the resection. The histopathological findings and patient and tumour characteristics were compared to those of a historical cohort (2009-2014) of conventional mandibular continuity resections. RESULTS: Twenty-four patients were included in the cohort. The average deviation from planned resection was found to be 2.2 mm. Histopathologic analysis confirmed all resection planes (bone) were tumour free, compared to 96.4% in the historic cohort. CONCLUSION: MRI-CT base tumour visualisation and 3D resection planning is a safe and accurate method for oncologic resection of the mandible. It is an improvement on the current methods reported for 3D resection planning based solely on CT data.