Physical examination during chemoradiation predicts outcome of locally advanced head and neck cancer. Secondary results of a randomized phase III trial (SAKK 10/94)

OBJECTIVES To analyze the prognostic value of clinical tumor response during chemoradiation for locally advanced head and neck cancer. PATIENTS AND METHODS The locoregional response at 50.4Gy was assessed by physical examination (PE) in patients treated within the randomized trial SAKK 10/94 using hyperfractionated radiotherapy (RT), median total dose 74.4Gy with or without cisplatin 20mg/m(2) chemotherapy on 5 consecutive days during weeks 1 and 5 or 6 of RT. Response was classified as a complete response (CR), complete response with uncertainty (Cru), partial response (PR), stable disease (SD), or progressive disease (PD). The primary endpoint was time to treatment failure (TTF) due to any cause. Secondary endpoints included locoregional-recurrence-free survival (LRRFS), distant metastasis-free survival (DMFS) and overall survival (OS). Univariate and multivariate Cox proportional hazards (PH) models were applied to analyze the associations between survival endpoints and clinical tumor response. RESULTS A total of 136, 131 and 97 patients were evaluable for response at the primary tumor, lymph nodes and both sites combined, respectively. At 50.4Gy 57/136 (42%), 46/131 (35%) and 21/97 (22%) patients had a good response (CR/Cru vs. PR/SD) at the primary tumor, the lymph nodes, and both sites combined, respectively. The median follow-up times were 11.4, 9.6 and 11.4years for the three groups. Good responses were all significantly associated with improved TTF, LRRFS, DMFS and OS in univariate analysis whereas good response at the primary tumor and lymph nodes remained significantly associated with TTF and OS after multivariate Cox PH models. CONCLUSIONS Locoregional response at 50.4Gy was identified as predictor of oncologic outcome. PE during treatment should not be underestimated in clinical practice.

Taxane-containing induction chemotherapy followed by definitive chemoradiotherapy. Outcome in patients with locally advanced head and neck cancer

BACKGROUND Induction chemotherapy followed by definitive chemoradiotherapy is an intensified treatment approach for locally advanced squamous cell carcinoma of the head and neck (HNSCC) that might be associated with high rates of toxicity. MATERIALS AND METHODS The data of 40 consecutive patients who underwent induction chemotherapy with docetaxel-containing regimens followed by intensity-modulated radiotherapy (IMRT) and concomitant systemic therapy for unresectable locally advanced HNSCC were retrospectively analyzed. Primary objectives were RT-related acute and late toxicity. Secondary objectives were response to induction chemotherapy, locoregional recurrence-free survival (LRRFS), overall survival (OS), and influencing factors for LRRFS and OS. RESULTS The median follow-up for surviving patients was 21 months (range, 2-53 months). Patients received a median of three cycles of induction chemotherapy followed by IMRT to 72 Gy. Three patients died during induction chemotherapy and one during chemoradiotherapy. Acute RT-related toxicity was of grade 3 and 4 in 72 and 3 % of patients, respectively, mainly dysphagia and dermatitis. Late RT-related toxicity was mainly xerostomia and bone/cartilage necrosis and was of grade 3 and 4 in 15 % of patients. One- and 2-year LRRFS and OS were 72 and 49 % and 77 and 71 %, respectively. CONCLUSION Induction chemotherapy followed by chemoradiotherapy using IMRT was associated with a high rate of severe acute and late RT-related toxicities in this selected patient cohort. Four patients were lost because of fatal complications. Induction chemotherapy did not compromise the delivery of full-dose RT; however, the use of three cycles of concomitant cisplatin was impaired.

One-year head to head comparison of the neointimal response between sirolimus eluting stent with reservoir technology and everolimus eluting stent: an optical coherence tomography study

OBJECTIVE to compare the vascular healing process between the sirolimus-eluting NEVO and the everolimus-eluting Xience stent by optical coherence tomography (OCT) at 1-year follow-up. BACKGROUND Presence of durable polymer on a drug-eluting metallic stent may be the basis of an inflammatory reaction with abnormal healing response. The NEVO stent, having a bioresorbable polymer eluted by reservoir technology, may overcome this problem. METHODS All consecutive patients, who received NEVO or Xience stent implantation between September 2010 and October 2010 in our institution, were included. Vascular healing was assessed at 1-year as percentage of uncovered struts, neointimal thickness (NIT), in-stent/stent area obstruction and pattern of neointima. RESULTS A total 47 patients (2:1 randomization, n = 32 NEVO, n = 15 Xience) were included. Eighteen patients underwent angiographic follow-up (eight patients with nine lesions for NEVO vs. 10 patients with 11 lesions for Xience). The angiographic late loss was numerically higher but not statistically different in NEVO compared with Xience treated lesions (0.38 ± 0.47 mm vs. 0.18 ± 0.27 mm; P = 0.171). OCT analysis of 4,912 struts demonstrated similar rates of uncovered struts (0.5 vs. 0.7%, P = 0.462), higher mean NIT (177.76 ± 87.76 µm vs. 132.22 ± 30.91 µm; P = 0.170) and in stent/stent area obstruction (23.02 ± 14.74% vs. 14.17 ± 5.94%, P = 0.120) in the NEVO as compared with Xience. CONCLUSION The NEVO stent with a reservoir technology seems to exhibit more neointimal proliferation as compared to Xience stent. The findings of our study, which currently represent the unique data existing on this reservoir technology, would need to be confirmed in a large population.

Correlation between subjective evaluation of symptoms and objective findings in early recurrent head and neck squamous cell carcinoma

IMPORTANCE This study addresses the value of patients' reported symptoms as markers of tumor recurrence after definitive therapy for head and neck squamous cell carcinoma. OBJECTIVE To evaluate the correlation between patients' symptoms and objective findings in the diagnosis of local and/or regional recurrences of head and neck squamous cell carcinomas in the first 2 years of follow-up. DESIGN Retrospective single-institution study of a prospectively collected database. SETTING Regional hospital. PARTICIPANTS We reviewed the clinical records of patients treated for oral cavity, oropharyngeal, laryngeal, and hypopharyngeal carcinomas between January 1, 2008, and December 31, 2009, with a minimum follow-up of 2 years. MAIN OUTCOMES AND MEASURES Correlation between symptoms and oncologic status (recurrence vs remission) in the posttreatment period. RESULTS Of the 101 patients included, 30 had recurrences. Pain, odynophagia, and dysphonia were independently correlated with recurrence (odds ratios, 16.07, 11.20, and 5.90, respectively; P < .001). New-onset symptoms had the best correlation with recurrences. Correlation was better between 6 to 12 and 18 to 21 months after therapy and in patients initially treated unimodally (P < .05). Primary stage and tumor site had no effect. CONCLUSIONS AND RELEVANCE The correlation between symptoms and oncologic status is low during substantial periods within the first 2 years of follow-up. New-onset symptoms, especially pain, odynophagia, or dysphonia, better correlate with tumor recurrence, especially in patients treated unimodally.

Adenosquamous carcinoma of the head and neck: report of 20 cases and review of the literature

PURPOSE To assess the clinical profile and prognostic factors in patients with adenosquamous carcinoma (ASC) of the head and neck treated by surgery and/or radiation therapy with or without chemotherapy. METHODS Data from 20 patients with stage I-II (n = 4), III (n = 5), or IVA (n = 11) head and neck ASC, treated between 1989 and 2010 were collected in a retrospective multicenter Rare Cancer Network study. Surgery was performed in 16 patients. Seventeen patients received combined modality treatment. RESULTS After a median follow-up of 15.5 months, 12 patients recurred. The 3-year and median overall survival, disease-free survival (DFS), and loco-regional control were 52% and 39 months, 32% and 12 months, and 47% and 33 months respectively. In multivariate analysis, DFS was negatively influenced by the presence of extracapsular extension and advanced stage. CONCLUSION Overall prognosis of locoregionally advanced ASC remains poor. However, early stage ASC patients managed with combined modality treatment may have prolonged DFS.

Investigations on an egyptian coffin and mummified head from Burgdorf Museum, Switzerland - A case of a historical puzzle

In the Burgdorf Museum of Ethnology, a mummy rests in a coffin. According to the inventory book, it was purchased from the Cairo Egyptian museum in 1926. The coffin was now examined by Egyptologists and the mummy was radiocarbon dated and examined by Anthropologists. The aim of the study was to compare the results and to check whether mummy and coffin actually belong together. The skull was examined morphological-anthropologically and by CT as a “blank sample”. Coffin and skull imply that the individual was female. The coffin dates to the Ptolemaic period. Only skull bones are preserved, the ethmoid is damaged. CT images Show resinous substances, bone fragments and brain remnants inside the skull. The ethmoid bone was probably foraminated during the mummification process and thus ended up inside the skull. The individual was mummified between the New Kingdom and the Ptolemaic period. Due to its style, it is most probable that the coffin comes from the Gamhud necropolis. The Burgdorf museum of ethnology inventory book chronicles were largely falsified by the examinations. There is a time gap between coffin and the mummy, there are two possible interpretations: the body was mummified with older linen, or the mummy and the coffin do not belong together. The authors strongly advise further investigations.

Collagenous Myofibroblastic Tumor of the Mandible: Case Report of a Unique Locally Aggressive Neoplasm Journal Head and Neck Pathology

We report a locally aggressive collagenous myofibroblastic neoplasm of the mandible in an 18-year-old male. Clinically, the lesion presented with rapid growth and irregular mandibular bone destruction. Grossly, the tumor was 10 cm in greatest dimension, light-tan, firm, and involving the posterior one-thirds of the body and inferior half of the left mandibular ramus. Histologically, the lesion was composed of a loose spindle cell proliferation interspersed with periodic dense bands of collagen. The spindle cells reacted positively to smooth muscle actin, calponin, and focally to desmin and were negative for S-100, pan-cytokeratin, CD99, CD34 and caldesmon, supporting myofibroblastic derivation. At our 4 year follow-up, the patient remained free of local recurrence and surgery related complications. The clinicopathologic findings and the differential diagnosis of this lesion is presented and discussed.

Dose Reduction in Standard Head CT: First Results from a New Scanner Using Iterative Reconstruction and a New Detector Type in Comparison with Two Previous Generations of Multi-slice CT

PURPOSE Computed tomography (CT) accounts for more than half of the total radiation exposure from medical procedures, which makes dose reduction in CT an effective means of reducing radiation exposure. We analysed the dose reduction that can be achieved with a new CT scanner [Somatom Edge (E)] that incorporates new developments in hardware (detector) and software (iterative reconstruction). METHODS We compared weighted volume CT dose index (CTDIvol) and dose length product (DLP) values of 25 consecutive patients studied with non-enhanced standard brain CT with the new scanner and with two previous models each, a 64-slice 64-row multi-detector CT (MDCT) scanner with 64 rows (S64) and a 16-slice 16-row MDCT scanner with 16 rows (S16). We analysed signal-to-noise and contrast-to-noise ratios in images from the three scanners and performed a quality rating by three neuroradiologists to analyse whether dose reduction techniques still yield sufficient diagnostic quality. RESULTS CTDIVol of scanner E was 41.5 and 36.4 % less than the values of scanners S16 and S64, respectively; the DLP values were 40 and 38.3 % less. All differences were statistically significant (p < 0.0001). Signal-to-noise and contrast-to-noise ratios were best in S64; these differences also reached statistical significance. Image analysis, however, showed "non-inferiority" of scanner E regarding image quality. CONCLUSIONS The first experience with the new scanner shows that new dose reduction techniques allow for up to 40 % dose reduction while still maintaining image quality at a diagnostically usable level.

Monitoring of threo-methylphenidate enantiomers in oral fluid by capillary electrophoresis with head-column field-amplified sample injection

Threo-methylphenidate is a chiral psychostimulant drug widely prescribed to treat attention-deficit hyperactivity disorder in children and adolescents. An enantioselective CE-based assay with head-column field-amplified sample stacking for analysis of threo-methylphenidate enantiomers in liquid/liquid extracts of oral fluid is described. Analytes are electrokinetically injected across a short water plug placed at the capillary inlet and become stacked at the interface between plug and buffer. Enantiomeric separation occurs within a few minutes in a pH 3.0 phosphate/triethanolamine buffer containing 20 mg/mL (2-hydroxypropyl)-β-CD as chiral selector. The assay with six point multilevel internal calibration provides a linear response for each enantiomer in the 10-200 ng/mL concentration range, is simple, inexpensive, and reproducible, and has an LOQ of 5 ng/mL. It was applied to oral fluid patient samples that were collected up to 12 h after intake of an immediate release tablet and two different extended release formulations with racemic methylphenidate. Drug profiles could thereby be assessed in a stereoselective way. Almost no levorotary threo-methylphenidate enantiomer was detected after intake of the two extended release formulations, whereas this enantiomer was detected during the first 2.5 h after intake of the immediate release preparation. The noninvasive collection of oral fluid is an attractive alternative to plasma for the monitoring of methylphenidate exposure in the pediatric community.

Street crossing behavior in younger and older pedestrians: an eye- and head-tracking study

BACKGROUND: Crossing a street can be a very difficult task for older pedestrians. With increased age and potential cognitive decline, older people take the decision to cross a street primarily based on vehicles' distance, and not on their speed. Furthermore, older pedestrians tend to overestimate their own walking speed, and could not adapt it according to the traffic conditions. Pedestrians' behavior is often tested using virtual reality. Virtual reality presents the advantage of being safe, cost-effective, and allows using standardized test conditions. METHODS: This paper describes an observational study with older and younger adults. Street crossing behavior was investigated in 18 healthy, younger and 18 older subjects by using a virtual reality setting. The aim of the study was to measure behavioral data (such as eye and head movements) and to assess how the two age groups differ in terms of number of safe street crossings, virtual crashes, and missed street crossing opportunities. Street crossing behavior, eye and head movements, in older and younger subjects, were compared with non-parametric tests. RESULTS: The results showed that younger pedestrians behaved in a more secure manner while crossing a street, as compared to older people. The eye and head movements analysis revealed that older people looked more at the ground and less at the other side of the street to cross. CONCLUSIONS: The less secure behavior in street crossing found in older pedestrians could be explained by their reduced cognitive and visual abilities, which, in turn, resulted in difficulties in the decision-making process, especially under time pressure. Decisions to cross a street are based on the distance of the oncoming cars, rather than their speed, for both groups. Older pedestrians look more at their feet, probably because of their need of more time to plan precise stepping movement and, in turn, pay less attention to the traffic. This might help to set up guidelines for improving senior pedestrians' safety, in terms of speed limits, road design, and mixed physical-cognitive trainings.

Impact of weight loss on survival after chemoradiation for locally advanced head and neck cancer: secondary results of a randomized phase III trial (SAKK 10/94).

BACKGROUND To analyze the impact of weight loss before and during chemoradiation on survival outcomes in patients with locally advanced head and neck cancer. METHODS From 07/1994-07/2000 a total of 224 patients with squamous cell carcinoma of the head and neck were randomized to either hyperfractionated radiation therapy alone or the same radiation therapy combined with two cycles of concomitant cisplatin. The primary endpoint was time to any treatment failure (TTF); secondary endpoints were locoregional recurrence-free survival (LRRFS), distant metastasis-free survival (DMFS) and overall survival (OS). Patient weight was measured 6 months before treatment, at treatment start and treatment end. RESULTS The proportion of patients with >5% weight loss was 32% before, and 51% during treatment, and the proportion of patients with >10% weight loss was 12% before, and 17% during treatment. After a median follow-up of 9.5 years (range, 0.1 - 15.4 years) weight loss before treatment was associated with decreased TTF, LRRFS, DMFS, cancer specific survival and OS in a multivariable analysis. However, weight loss during treatment was not associated with survival outcomes. CONCLUSIONS Weight loss before and during chemoradiation was commonly observed. Weight loss before but not during treatment was associated with worse survival.

VOR gain by head impulse video-oculography differentiates acute vestibular neuritis from stroke

OBJECTIVE Vestibular neuritis is often mimicked by stroke (pseudoneuritis). Vestibular eye movements help discriminate the two conditions. We report vestibulo-ocular reflex (VOR) gain measures in neuritis and stroke presenting acute vestibular syndrome (AVS). METHODS Prospective cross-sectional study of AVS (acute continuous vertigo/dizziness lasting >24 h) at two academic centers. We measured horizontal head impulse test (HIT) VOR gains in 26 AVS patients using a video HIT device (ICS Impulse). All patients were assessed within 1 week of symptom onset. Diagnoses were confirmed by clinical examinations, brain magnetic resonance imaging with diffusion-weighted images, and follow-up. Brainstem and cerebellar strokes were classified by vascular territory-posterior inferior cerebellar artery (PICA) or anterior inferior cerebellar artery (AICA). RESULTS Diagnoses were vestibular neuritis (n = 16) and posterior fossa stroke (PICA, n = 7; AICA, n = 3). Mean HIT VOR gains (ipsilesional [standard error of the mean], contralesional [standard error of the mean]) were as follows: vestibular neuritis (0.52 [0.04], 0.87 [0.04]); PICA stroke (0.94 [0.04], 0.93 [0.04]); AICA stroke (0.84 [0.10], 0.74 [0.10]). VOR gains were asymmetric in neuritis (unilateral vestibulopathy) and symmetric in PICA stroke (bilaterally normal VOR), whereas gains in AICA stroke were heterogeneous (asymmetric, bilaterally low, or normal). In vestibular neuritis, borderline gains ranged from 0.62 to 0.73. Twenty patients (12 neuritis, six PICA strokes, two AICA strokes) had at least five interpretable HIT trials (for both ears), allowing an appropriate classification based on mean VOR gains per ear. Classifying AVS patients with bilateral VOR mean gains of 0.70 or more as suspected strokes yielded a total diagnostic accuracy of 90%, with stroke sensitivity of 88% and specificity of 92%. CONCLUSION Video HIT VOR gains differ between peripheral and central causes of AVS. PICA strokes were readily separated from neuritis using gain measures, but AICA strokes were at risk of being misclassified based on VOR gain alone.

Serial [18F]-fluoromisonidazole PET during radiochemotherapy for locally advanced head and neck cancer and its correlation with outcome.

PURPOSE The aim was to assess changes of tumour hypoxia during primary radiochemotherapy (RCT) for head and neck cancer (HNC) and to evaluate their relationship with treatment outcome. MATERIAL AND METHODS Hypoxia was assessed by FMISO-PET in weeks 0, 2 and 5 of RCT. The tumour volume (TV) was determined using FDG-PET/MRI/CT co-registered images. The level of hypoxia was quantified on FMISO-PET as TBRmax (SUVmaxTV/SUVmean background). The hypoxic subvolume (HSV) was defined as TV that showed FMISO uptake ⩾1.4 times blood pool activity. RESULTS Sixteen consecutive patients (T3-4, N+, M0) were included (mean follow-up 31, median 44months). Mean TBRmax decreased significantly (p<0.05) from 1.94 to 1.57 (week 2) and 1.27 (week 5). Mean HSV in week 2 and week 5 (HSV2=5.8ml, HSV3=0.3ml) were significantly (p<0.05) smaller than at baseline (HSV1=15.8ml). Kaplan-Meier plots of local recurrence free survival stratified at the median TBRmax showed superior local control for less hypoxic tumours, the difference being significant at baseline and after 2weeks (p=0.031, p=0.016). CONCLUSIONS FMISO-PET documented that in most HNC reoxygenation starts early during RCT and is correlated with better outcome.

If hunters end up in the emergency room: a retrospective analysis of hunting injuries in a swiss emergency department.

Aim. to characterize the mechanisms, patterns, and outcomes of nonfatal hunting-related injuries in patients presenting to Bern University Hospital, Switzerland, and compare these to reports of hunting injuries worldwide. Methods. patients presenting with hunting-related injuries to the Emergency Department at Bern University hospital from 2000 to 2014 were identified by retrospectively searching the department database using the keyword "hunt." Each case was analyzed in terms of the patient age and gender, the mechanism and pattern of injury, and management and patient follow-up. Results. 19 patients were identified. 16 were male with a mean age of 50 years (range: 16-74). Mechanisms of injury included firearm-related injuries, falls, and knife wounds. The most common patterns of injury were head injuries (7), followed by injuries to the upper (5) or lower limb (5) and trunk (2). Over half of the patients were admitted, and nine required emergency surgery. Conclusion. Nonfatal hunting accidents in Bern, Switzerland, are largely caused by firearms and falls and tend to occur in male hunters with a mean age of 50 years. The most common patterns of injury are orthopedic and head injuries, often requiring surgery. These findings are consistent with international studies of nonfatal hunting accidents.

Hole in the Head: a Play, Accompanied by a Conspectus of Knowledge, Both Repressed and Researched, that Directly Influenced the Playwright in Her Development of a New Work

"Hole in the Head" is a play about a woman who wakes up. Maude wakes up in the first act, and in every subsequent scene she undergoes some form of physical or emotional awakening as characters walk in and out of her front door."Hole in the Head" is accompanied by an introduction that attempts to understand the interplay between creativity and academia through an analysis of theatre, feminist and queer theory, and science.