Current aspects of the quality of head and neck cancer care - survey of the Scandinavian Society for Head and Neck Oncology.

BACKGROUND: All Nordic countries have national cancer registries collecting data on head and neck cancer (HNC) incidence and survival. However, there is a lack of consensus on how other quality aspects should be monitored. AIMS: We conducted a web-based survey to find opportunities for quality control and improvement. METHODS: A web-based survey was sent to one otorhinolaryngology - head and neck (ORL-HN) surgeon, and one oncologist at each Nordic university hospital treating HNC. In total, 42 responses from all 21 university hospitals were included. RESULTS: In over half of the university hospitals, an oncologist, an ORL-HN surgeon, a pathologist, a radiologist, and a specialized nurse was always present at the multidisciplinary tumor board (MTB) meeting. Of 42 respondents 35 (83%) agreed that treatment delays were systematically recorded for each patient. Eleven of 21 (52%) oncologists agreed that side-effects of (chemo)radiotherapy were systematically recorded. Less than half of the respondents agreed that complications of surgery, and post-treatment quality of life (QOL) were systematically recorded. CONCLUSIONS: In the Nordic countries, the importance of HNC treatment timelines is well acknowledged. There is a lack of consensus on the composition of MTB meeting, and how treatment-related morbidity should be monitored outside clinical trials.

Treatment and outcome among patients with laryngeal squamous cell carcinoma in Stockholm-A population-based study.

Objective: Survival of patients with advanced laryngeal squamous cell carcinoma (LSCC) remains poor and management protocols warrant further development. We thus investigated treatment and outcome-related factors for LSCC in Stockholm, Sweden. Methods: In a retrospective setting, 520 patients with LSCC diagnosed during 2000-2014, were included. Data on stage, treatment, and outcome were correlated with recurrence-free and overall survival (RFS and OS, respectively). Results: Five-year OS for all patients was 65%. Five-year RFS for T1a, T1b, T2, T3, and T4 glottic LSCC was 90%, 91%, 77%, 47%, and 80%, respectively. The corresponding figures for T1, T2, T3, and T4 supraglottic LSCC were 64%, 66%, 64%, and 86%. Conclusion: Patients with a T3 glottic LSCC had unexpectedly poor survival, especially when compared with patients with a T4 tumor. Patients with T4 disease were primarily treated with laryngectomy and postoperative radiotherapy (RT)/chemoradiotherapy (CRT), while most patients with T3 LSCC were treated with RT/CRT.

Postsurgical pyoderma gangrenosum and flap necrosis in a head and neck cancer patient following neck dissection.

Postsurgical pyoderma gangrenosum (PSPG) develops in the skin after surgery without known cause. Immunosuppression constitutes first-line therapy and increases the likelihood of successful surgery when needed. PSPG should be considered when a flap necrosis occurs.

A descriptive study highlighting the differences in the treatment protocol for oral tongue cancer in Sweden and Finland.

Background and aims: Stage II cancer of the tongue is mostly managed surgically both locally and regionally. However, indications for postoperative radiotherapy and reconstructive options vary between centers. This paper aims to describe differences in treatment in a geographically homogenous cohort.Methods: A retrospective comparison was made between two cohorts of clinical T2N0 tongue cancer from Finland and Sweden. The Finnish cohort included 75 patients and the Swedish 54. All patients had curative intent of treatment and no previous head and neck cancer. Data analyzed consisted of pathological stage, size and thickness of tumor, frequency of reconstruction, radiotherapy delivered, and survival.Results: The Finnish cohort included a higher proportion of patients managed with reconstructive surgery (67%) than the Swedish cohort (0%), p < .00001. More patients were treated with postoperative radiotherapy (84%) in the Swedish cohort than in the Finnish (54%), p < .0002. The Finnish cohort had a higher level of survival and included more frequent downstaging (cTNM to pTNM).Conclusions and significance: Our data indicate a major difference in the management of T2N0 oral tongue cancer. The optimal cut-off size and growth pattern of the tumor warranting reconstruction should be further evaluated in a prospective manner considering both survival and quality of life.

Survival, migration, and differentiation of Sox1-GFP embryonic stem cells in coculture with an auditory brainstem slice preparation.

The poor regeneration capability of the mammalian hearing organ has initiated different approaches to enhance its functionality after injury. To evaluate a potential neuronal repair paradigm in the inner ear and cochlear nerve we have previously used embryonic neuronal tissue and stem cells for implantation in vivo and in vitro. At present, we have used in vitro techniques to study the survival and differentiation of Sox1-green fluorescent protein (GFP) mouse embryonic stem (ES) cells as a monoculture or as a coculture with rat auditory brainstem slices. For the coculture, 300 microm-thick brainstem slices encompassing the cochlear nucleus and cochlear nerve were prepared from postnatal SD rats. The slices were propagated using the membrane interface method and the cochlear nuclei were prelabeled with DiI. After some days in culture a suspension of Sox1 cells was deposited next to the brainstem slice. Following deposition Sox1 cells migrated toward the brainstem and onto the cochlear nucleus. GFP was not detectable in undifferentiated ES cells but became evident during neural differentiation. Up to 2 weeks after transplantation the cocultures were fixed. The undifferentiated cells were evaluated with antibodies against progenitor cells whereas the differentiated cells were determined with neuronal and glial markers. The morphological and immunohistochemical data indicated that Sox1 cells in monoculture differentiated into a higher percentage of glial cells than neurons. However, when a coculture was used a significantly lower percentage of Sox1 cells differentiated into glial cells. The results demonstrate that a coculture of Sox1 cells and auditory brainstem present a useful model to study stem cell differentiation.

Regional recurrence in early stage I-II oral tongue cancer: a single institutional study and review of the literature.

CONCLUSIONS: There is a high propensity for locoregional and isolated regional failure in stage II patients, even though treated with combined therapy. In stage I patients the risk of isolated regional failure was moderate, at levels below 10%. BACKGROUND: The neck treatment of early stages of oral tongue squamous cell carcinoma (OTSCC) are still debatable, considering that previous studies have produced diverting results. The purpose of this study is to report on the outcome of patients with stages I-II, with special respect to regional outcome. MATERIALS AND METHODS: All patients treated for OTSCC at Karolinska University Hospital between 2008-2014 were included. Patient demographics, intention of treatment, treatment modality, time of follow-up and status at follow-up, recurrence, and place of recurrence were recorded. RESULTS: Of 230 patients, 149 presented within stages I and II. Of those, 105 were electively treated to the neck. In stage I, the risk of presence of disease in the neck specimen was four out of 63 (6%), whereas 17 out of 41 (41%) were positive in stage II patients. The overall risk of isolated regional failure at any time in stage I patients was six out of 89 and in stage II 25 out of 60.

WRAP53ß, survivin and p16INK4a expression as potential predictors of radiotherapy/chemoradiotherapy response in T2N0-T3N0 glottic laryngeal cancer.

The current treatment recommendation for T2-3N0M0 glottic squamous cell carcinoma (SCC) in the Nordic countries comprises of radiotherapy (RT) and chemoradiotherapy (CRT). Tumor radiosensitivity varies and another option is primary surgical treatment, which underlines the need for predictive markers in this patient population. The aim of the present study was to investigate the relation of the proteins WRAP53ß, survivin and p16INK4a to RT/CRT response and ultimate outcome of patients with T2-T3N0 glottic SCC. Protein expression was determined using immunohistochemistry on tumors from 149 patients consecutively treated with RT or CRT at Helsinki University Hospital, Karolinska University Hospital, and Linköping University Hospital during 1999-2010. Our results demonstrate a significantly better 5-year relapse-free survival, disease-free survival (DFS), disease-specific survival and overall survival of patients with T3N0 tumors treated with CRT compared with RT alone. Patients with tumors showing a cytoplasmic staining of WRAP53ß revealed significantly worse DFS compared with those with nuclear staining. For survivin, we observed a trend towards better 5-year DFS in patients with strong nuclear survivin expression compared with those with weak nuclear survivin expression (p=0.091). Eleven (7%) tumors showed p16 positivity, with predilection to younger patients, and this age group of patients with p16-positive SCC had a significantly better DFS compared with patients with p16-negative SCC. Taken together, our results highlight WRAP53ß as a potential biomarker for predicting RT/CRT response in T2-T3N0 glottic SCC. p16 may identify a small but distinct group of glottic SCC with favorable outcome. Furthermore, for T3N0 patients better outcome was observed following CRT compared to RT alone.

BDNF increases survival and neuronal differentiation of human neural precursor cells cotransplanted with a nanofiber gel to the auditory nerve in a rat model of neuronal damage.

OBJECTIVES: To study possible nerve regeneration of a damaged auditory nerve by the use of stem cell transplantation. METHODS: We transplanted HNPCs to the rat AN trunk by the internal auditory meatus (IAM). Furthermore, we studied if addition of BDNF affects survival and phenotypic differentiation of the grafted HNPCs. A bioactive nanofiber gel (PA gel), in selected groups mixed with BDNF, was applied close to the implanted cells. Before transplantation, all rats had been deafened by a round window niche application of ß-bungarotoxin. This neurotoxin causes a selective toxic destruction of the AN while keeping the hair cells intact. RESULTS: Overall, HNPCs survived well for up to six weeks in all groups. However, transplants receiving the BDNF-containing PA gel demonstrated significantly higher numbers of HNPCs and neuronal differentiation. At six weeks, a majority of the HNPCs had migrated into the brain stem and differentiated. Differentiated human cells as well as neurites were observed in the vicinity of the cochlear nucleus. CONCLUSION: Our results indicate that human neural precursor cells (HNPC) integration with host tissue benefits from additional brain derived neurotrophic factor (BDNF) treatment and that these cells appear to be good candidates for further regenerative studies on the auditory nerve (AN).

Survival, migration and differentiation of mouse tau-GFP embryonic stem cells transplanted into the rat auditory nerve.

Stem cells have been investigated as treatment for a variety of diagnoses such as Parkinson's disease, Alzheimer's disease and spinal cord injuries. Here, we investigated the possibility of using stem cells as a replacement therapy for lesions of the auditory nerve (AN). We transplanted tau-GFP mouse embryonic stem cells into the AN either by the internal auditory meatus or via the modiolus in rats that had been previously deafened by application of ß-bungarotoxin to the round window niche. We investigated the effect of brain derived neurotrophic factor (BDNF) on cell transplant survival and differentiation. Additionally chondroitinase ABC (ChABC), a digestive enzyme that cleaves the core chondroitin sulfate proteoglycans, was used in order to promote possible migration of cells and axons through the transitional zone. A bioactive isoleucine-lysine-valine-alanine-valine (IKVAV) peptide amphiphile (PA) nanofiber gel was applied around the cell injection site. This nanofiber gel has been shown to promote neural differentiation and other similar gels have been used to encapsulate and release proteins. Three weeks after injection, transplanted cells were found in the scala tympani, the modiolus, the AN trunk and the brain stem. As compared to cell transplantation and gel only, BDNF content in the PA gel increased cell survival and neuronal differentiation. In the animals treated with ChABC we observed extensive migration of cells through the transitional zone to or from the CNS.

Horseradish peroxidase dye tracing and embryonic statoacoustic ganglion cell transplantation in the rat auditory nerve trunk.

At present severe damage to hair cells and sensory neurons in the inner ear results in non-treatable auditory disorders. Cell implantation is a potential treatment for various neurological disorders and has already been used in clinical practice. In the inner ear, delivery of therapeutic substances including neurotrophic factors and stem cells provide strategies that in the future may ameliorate or restore hearing impairment. In order to describe a surgical auditory nerve trunk approach, in the present paper we injected the neuronal tracer horseradish peroxidase (HRP) into the central part of the nerve by an intra cranial approach. We further evaluated the applicability of the present approach by implanting statoacoustic ganglion (SAG) cells into the same location of the auditory nerve in normal hearing rats or animals deafened by application of ß-bungarotoxin to the round window niche. The HRP results illustrate labeling in the cochlear nucleus in the brain stem as well as peripherally in the spiral ganglion neurons in the cochlea. The transplanted SAGs were observed within the auditory nerve trunk but no more peripheral than the CNS-PNS transitional zone. Interestingly, the auditory nerve injection did not impair auditory function, as evidenced by the auditory brainstem response. The present findings illustrate that an auditory nerve trunk approach may well access the entire auditory nerve and does not compromise auditory function. We suggest that such an approach might compose a suitable route for cell transplantation into this sensory cranial nerve.

beta-Bungarotoxin application to the round window: an in vivo deafferentation model of the inner ear.

Hearing impairment can be caused by a primary lesion to the spiral ganglion neurons (SGNs) with the hair cells kept intact, for example via tumours, trauma or auditory neuropathy. To mimic these conditions in animal models various methods of inflicting damage to the inner ear have been used. However, only a few methods have a selective effect on the SGNs, which is of importance since it might be clinically more relevant to study hearing impairment with the hair cells undamaged. beta-Bungarotoxin is a venom of the Taiwan banded krait, which in vitro has been shown to induce apoptosis in neurons, leaving remaining cochlear cells intact. We wanted to create an in vivo rat model of selective damage to primary auditory neurons. Under deep anaesthesia, 41 rats received beta-Bungarotoxin or saline to the round window niche. At postoperative intervals between days 3 and 21 auditory brainstem response (ABR) measurement, immunohistochemistry, SGN quantification and cochlear surface preparation were performed. The results in the beta-Bungarotoxin-treated ears, as compared with sham-operated ears, show significantly increased ABR thresholds at all postoperative intervals, illustrating a severe to profound hearing loss at all tested frequencies (3.5, 7, 16 and 28 kHz). Quantification of the SGNs showed no obvious reduction in neuronal numbers until 14 days postoperatively. Between days 14 and 21 a significant reduction in SGN numbers was observed. Cochlear surface preparation and immunohistochemistry showed that the hair cells were intact. Our results illustrate that in vivo application of beta-Bungarotoxin to the round window niche is a feasible way of deafening rats by SGN reduction while the hair cells are kept intact.