Validation of skeletal muscle mass assessment at the level of the third cervical vertebra in patients with head and neck cancer.

BACKGROUND: Low skeletal muscle mass (SMM) is associated with adverse outcomes. SMM is often assessed at the third lumbar vertebra (L3) on abdominal imaging. Abdominal imaging is not routinely performed in patients with head and neck cancer (HNC). We aim to validate SMM measurement at the level of the third cervical vertebra (C3) on head and neck imaging. MATERIAL AND METHODS: Patients with pre-treatment whole-body computed tomography (CT) between 2010 and 2018 were included. Cross-sectional muscle area (CSMA) was manually delineated at the level of C3 and L3. Correlation coefficients and intraclass correlation coefficients (ICCs) were calculated. Cohen's kappa was used to assess the reliability of identifying a patient with low SMM. RESULTS: Two hundred patients were included. Correlation between CSMA at the level of C3 and L3 was good (r = 0.75, p < 0.01). Using a multivariate formula to estimate CSMA at L3, including gender, age, and weight, correlation improved (r = 0.82, p < 0.01). The agreement between estimated and actual CSMA at L3 was good (ICC 0.78, p < 0.01). There was moderate agreement in the identification of patients with low SMM based on the estimated lumbar skeletal muscle mass index (LSMI) and actual LSMI (Cohen's κ: 0.57, 95%CI 0.45-0.69). CONCLUSIONS: CSMA at C3 correlates well with CSMA at L3. There is moderate agreement in the identification of patients with low SMM based on the estimated lumbar SMI (based on measurement at C3) and actual LSMI.

Skeletal muscle mass is an imaging biomarker for decreased survival in patients with oropharyngeal squamous cell carcinoma.

OBJECTIVES: Low skeletal muscle mass (SMM) and sarcopenic obesity (co-presence of low SMM and obesity) are emerging prognosticators in oncology, but the prevalence and prognostic value in oropharyngeal squamous cell carcinoma (OPSCC) is not yet known. MATERIALS AND METHODS: Patients with OPSCC, curative treatment intention and pre-treatment diagnostic imaging of the head and neck area were included. Patients with unknown HPV-status, palliative treatment intention or unavailable imaging were excluded, Relevant demographic and clinical characteristics were collected between 2009 and 2016. Patients were stratified into a low-, intermediate-, and high-risk group according to HPV-status, amount of pack-years, tumor and nodal stage. SMM was radiologically measured and cutoff values were determined by optimal stratification. The prognostic value of low SMM and sarcopenic obesity for overall survival (OS) and disease-free survival (DFS) was determined by Cox regression analysis and Kaplan Meier survival curves. RESULTS: In 216 patients, low SMM and sarcopenic obesity were present in 140 (64.8%) and 13 (6.0%) patients, respectively. On multivariate analysis, stratification into a high-risk group (HPV-negative status with ≥10-pack-years or T4-stage) was a prognostic factor for OS and DFS (HR 2.93, p < 0.01) (HR 4.66, p < 0.01). Of specific interest, sarcopenic obesity was a strong negative prognostic factor for OS and DFS (HR 4.42, p < 0.01 and (HR 3.90, p < 0.05), independent from other well-known prognostic factors such as HPV-status. CONCLUSION: Low skeletal muscle mass is highly prevalent in OPSCC patients. Sarcopenic obesity is a novel pretreatment prognosticator for OS and DFS in OPSCC and should therefore be considered in clinical decision making.

Interobserver agreement of skeletal muscle mass measurement on head and neck CT imaging at the level of the third cervical vertebra.

OBJECTIVES: Skeletal muscle mass (SMM) is most often assessed in cancer patients on abdominal computed tomography (CT) imaging at the level of the third lumbar vertebra (L3). Abdominal CT imaging is not routinely performed in head and neck cancer (HNC) patients. Recently, a novel method to assess SMM on a single transversal CT slice at the level of the third cervical vertebra (C3) was published. The objective of this study was to assess the robustness of this novel C3 measurement method in terms of interobserver agreement. PATIENTS AND METHODS: Patients diagnosed with locally advanced head and neck squamous cell carcinoma (LA-HNSCC) at our center between 2007 and 2011 were evaluated. Fifty-four patients with were randomly selected for analysis. Six observers independently measured the cross-sectional muscle area (CSMA) at the level of C3 using a predefined, written protocol as instruction. Interobserver agreement was assessed using intraclass correlation coefficients (ICCs), a Bland-Altman plot and Fleiss' kappa (κ). RESULTS: The agreement in vertebra selection between all observers was excellent (Fleiss' κ: 0.96). There was a substantial agreement between all observers in single slice selection (Fleiss' κ: 0.61). For all CSMA measurements, ICCs were excellent (0.763-0.969; all p < 0.001). The Bland-Altman plot showed good agreement between measurements, with narrow limits of agreement. CONCLUSION: Interobserver agreement for SMM measurement at the level of C3 was excellent. Assessment of SMM at the level of C3 is easy and robust and can performed on routinely available imaging in HNC patients.

Systematic review of the diagnostic value of laryngeal stroboscopy in excluding early glottic carcinoma.

OBJECTIVE: Laryngeal stroboscopy is an important diagnostic tool in the work-up of patients with phoniatric complaints. The aim of this article was to evaluate the diagnostic value of laryngeal stroboscopy in excluding glottic carcinoma in patients with suspected glottic carcinoma. DATA SOURCES: PubMed, Embase and the Cochrane Library. REVIEW METHODS: A systematic literature search was performed in PubMed, Embase and the Cochrane Library. Studies reporting original study data were included. Studies were selected based on predefined inclusion and exclusion criteria and were consequently systematically assessed for their relevance and risk of bias. Studies with low relevance, high risk of bias or both were excluded from analysis. The prevalences, sensitivities, specificities and post-test probabilities of laryngeal stroboscopy for detecting glottic carcinoma were extracted or calculated with data supplied in the articles. RESULTS: Seven studies, with high relevance and moderate risk of bias, were selected for data extraction. The baseline risk of glottic carcinoma was 25-49% in the included studies. Sensitivity ranged between 80% and 100% and specificity between 25% and 100%. Post-test probabilities of malignancy in case of an abnormal stroboscopy ranged between 35% and 100%. Post-test probabilities of malignancy in case of a normal stroboscopy ranged between 0% and 29%. CONCLUSION: A normal laryngeal stroboscopic result predicts the absence of invasive carcinoma. Laryngeal stroboscopy can therefore be suggested as a useful supplemental examination in the standard diagnostic work-up for all patients with suspected glottic carcinoma.

A nation-wide epidemiological study on the risk of developing second malignancies in patients with different histological subtypes of nasopharyngeal carcinoma.

OBJECTIVE: Risk assessment of second head/neck and Epstein Barr Virus (EBV)-related malignancies in patients with different nasopharyngeal carcinoma (NPC) subtypes. METHODS: This is a cross-sectional study. Pathology records were retrieved from PALGA (a Dutch pathology registry database) between 1995 and 2013. Second primary malignancy (SPM) data was extracted from PALGA. Odds ratios (OR) for SPM in the head/neck, and the upper/lower airways were calculated using logistic regression. Pearson X(2)-test and Fisher's exact test were used to assess the relationship between NPC (and EBV-status) with SPM. Standardized incidence rates (SIR) were calculated. RESULTS: Histologically diagnosed NPC (keratinizing and undifferentiated and differentiated non-keratinizing subtypes) (n=1175) were identified. NPC patients have an increased risk of second head/neck malignancies (SIR 4.7 95% CI 3.3-6.5). Keratinizing NPCs have an OR of 1.947 (95% CI 1.362-2.782) for SPM, an OR of 4.026 (95% CI 2.308-7.023) for carcinomas of the upper/lower airways, an OR of 4.306 (95% CI 2.299-8.066) for head/neck malignancies, an OR of 5.289 (95% CI 2.740-10.211) for HNSCC with a SIR of 4.7 (95CI 3.3-6.5). Non-keratinizing NPCs also have an increased risk of head/neck malignancies with a SIR of 3.2 (95% CI 1.8-5.1), but less than keratinizing NPCs (p=<0.001). Positive EBV-status is not associated with (EBV-related) SPM. CONCLUSION: NPCs have a higher risk of SPM regardless of EBV status. SPM (especially HNSCC and malignancies of the upper aerodigestive tract) are more prevalent in keratinizing NPC compared to non-keratinizing NPC. Close clinical follow-up of NPC patients, with specific attention on SPM, is justified.

Oncological outcome and long-term complications in robot-assisted radical surgery for early stage cervical cancer: an observational cohort study.

OBJECTIVE: To report the oncological outcome and long-term complications of radical surgery by robot-assisted laparoscopy in early stage cervical cancer. DESIGN: Observational cohort study. SETTING: Tertiary referral centre. POPULATION: About 100 cervical cancer patients treated consecutively with robot-assisted radical surgery between 2008 and 2013. METHODS: Two gynaecological oncologists specialised in minimally invasive surgery performed all surgeries on a three/four-armed robotic system. Procedures consisted of pelvic lymph node dissection combined with a radical hysterectomy, radical vaginal trachelectomy or parametrectomy. MAIN OUTCOME MEASURES: Recurrence, survival and long-term complication rates. RESULTS: 104 robot-assisted laparoscopies were performed in 100 patients (stage IA1-IIB), with a median follow-up of 29.5 months (range 2.5-67.1 months). Thirteen cases were diagnosed with a loco-regional (8%), distant (4%) or combined (1%) recurrence at a median of 14.4 months (range 2.9-34.8 months). All mortality (7%) was cervical cancer-related and due to recurrent disease. Four recurrences receive palliative care and two are in complete remission. The overall 5-year progression-free and disease-specific survival rates are 81.4 and 88.7%, respectively. Frequent complications were lymphoedema (26%), lower urinary tract symptoms (19%), urinary tract infection (17%) and sexual disorders (9%). Five patients had a vaginal cuff dehiscence. No complication-related mortality occurred. CONCLUSION: The recurrence, survival and long-term complication rates of robot-assisted radical surgery for early stage cervical cancer in this cohort are reassuring concerning its continued clinical use.

Effect of oral contraceptives on lamotrigine levels depends on comedication.

OBJECTIVES: To evaluate prospectively the influence of cyclic oral contraceptive (OC) use on lamotrigine (LTG) serum levels when used in combination therapy. METHODS: Women with epilepsy using LTG in combination with valproate (VPA; n=7), carbamazepine (CBZ; n=3) or oxcarbazepine (OXC; n=1) were evaluated during two periods of 28 days cyclic OC use, monitoring antiepileptic drug (AED) levels every other day with the dried blood spot sampling method. Results were compared with women on LTG monotherapy and OCs (n=12). Pharmacokinetic analysis was performed using NONMEM software. RESULTS: Mean study population value of LTG clearance estimated by the final model was 3.17 l/h. Introduction of covariates for comedication (VPA, CBZ, OXC and OC) significantly reduced the between-subject variability. A significant influence of OC comedication on LTG clearance was seen in both LTG monotherapy (clearance with OC 4.02±0.38 l/h, OC-free week 3.03±0.39 l/h) and in LTG-CBZ combination (clearance with OC 4.95±0.15 l/h, OC-free week 4.15±0.26 l/h). No influence of OC was found in LTG-VPA combination (clearance with OC 0.99±0.16 l/h, OC-free week 0.90±0.15 l/h). CONCLUSIONS: Adding OCs to LTG monotherapy or the combination LTG-CBZ significantly increased the LTG clearance and thus reduced LTG serum levels. In the combination LTG-CBZ, OCs had a non-significant effect on CBZ clearance. No significant influence of cyclic OC use on LTG or VPA clearance was found when these AEDs were used in combination.

Magnetic tracking in the operation room using the da Vinci(®) telemanipulator is feasible.

In recent years, robotic assistance for surgical procedures has grown on a worldwide scale, particularly for use in more complex operations. Such operations usually require meticulous handling of tissue, involve a narrow working space and limit the surgeon's sense of orientation in the human body. Improvement in both tissue handling and working within a narrow working space might be achieved through the use of robotic assistance. Soft tissue navigation might improve orientation by visualizing important target and risk structures intraoperatively, thereby possibly improving patient outcome. Prerequisites for navigation are its integration into the surgical workflow and accurate localization of both the instruments and patient. Magnetic tracking allows for good integration but is susceptible to distortion through metal or electro-magnetic interference, which may be caused by the operation table or a robotic system. We have investigated whether magnetic tracking can be used in combination with the da Vinci(®) (DV) telemanipulator in terms of stability and precision. We used a common magnetic tracking system (Aurora(®), NDI Inc.) with the DV in a typical operation setup. Magnetic field distortion was evaluated using a measuring facility, with the following reference system: without any metal (R), operation table alone (T), DV in standby (D) and DV in motion (Dm). The maximum error of the entire tracking volume for R, T, D and Dm was 9.9, 32.8, 37.9 and 37.2 mm, respectively. Limiting the tracking volume to 190 mm (from cranial to caudal) resulted in a maximum error of 4.0, 8.3, 8.5 and 8.9 mm, respectively. When used in the operation room, magnetic tracking shows high errors, mainly due to the operation table. The target area should be limited to increase accuracy, which is possible for most surgical applications. The use of the da Vinci(®) telemanipulator only slightly aggravates the distortion and can thus be used in combination with magnetic tracking systems.

Statistical tracking of tree-like tubular structures with efficient branching detection in 3D medical image data.

The segmentation of tree-like tubular structures such as coronary arteries and airways is an essential step for many 3D medical imaging applications. Statistical tracking techniques for the extraction of elongated structures have received considerable attention in recent years due to their robustness against image noise and pathological changes. However, most tracking methods are limited to a specific application and do not support branching structures efficiently. In this work, we present a novel statistical tracking approach for the extraction of different types of tubular structures with ringlike cross-sections. Domain-specific knowledge is learned from training data sets and integrated into the tracking process by simple adaption of parameters. In addition, an efficient branching detection algorithm is presented. This approach was evaluated by extracting coronary arteries from 32 CTA data sets and distal airways from 20 CT scans. These data sets were provided by the organizers of the workshop '3D Segmentation in the Clinic: A Grand Challenge II-Coronary Artery Tracking (CAT08)' and 'Extraction of Airways from CT 2009 (EXACT'09)'. On average, 81.5% overlap and 0.51 mm accuracy for the tracking of coronary arteries were achieved. For the extraction of airway trees, 51.3% of the total tree length, 53.6% of the total number of branches and a 4.98% false positive rate were attained. In both experiments, our approach is comparable to state-of-the-art methods.

Standardized assessment of new electromagnetic field generators in an interventional radiology setting.

PURPOSE: Two of the main challenges associated with electromagnetic (EM) tracking in computer-assisted interventions (CAIs) are (1) the compensation of systematic distance errors arising from the influence of metal near the field generator (FG) or the tracked sensor and (2) the optimized setup of the FG to maximize tracking accuracy in the area of interest. Recently, two new FGs addressing these issues were proposed for the well-established Aurora(®) tracking system [Northern Digital, Inc. (NDI), Waterloo, Canada]: the Tabletop 50-70 FG, a planar transmitter with a built-in shield that compensates for metal distortions emanating from treatment tables, and the prototypical Compact FG 7-10, a mobile generator designed to be attached to mobile imaging devices. The purpose of this paper was to assess the accuracy and precision of these new FGs in an interventional radiology setting. METHODS: A standardized assessment protocol, which uses a precisely machined base plate to measure relative error in position and orientation, was applied to the two new FGs as well as to the well-established standard Aurora(®) Planar FG. The experiments were performed in two different settings: a reference laboratory environment and a computed tomography (CT) scanning room. In each setting, the protocol was applied to three different poses of the measurement plate within the tracking volume of the three FGs. RESULTS: The two new FGs provided higher precision and accuracy within their respective measurement volumes as well as higher robustness with respect to the CT scanner compared to the established FG. Considering all possible 5 cm distances on the grid, the error of the Planar FG was increased by a factor of 5.94 in the clinical environment (4.4 mm) in comparison to the error in the laboratory environment (0.8 mm). In contrast, the mean values for the two new FGs were all below 1 mm with an increase in the error by factors of only 2.94 (Reference: 0.3 mm; CT: 0.9 mm) and 1.04 (both: 0.5 mm) in the case of the Tabletop FG and the Compact FG, respectively. CONCLUSIONS: Due to their high accuracy and robustness, the Tabletop FG and the Compact FG could eliminate the need for compensation of EM field distortions in certain CT-guided interventions.

Differences between antigenic determinants of pig and cat zona pellucida proteins.

Despite many efforts, the control of reproduction in feral cat populations is still a problem in urban regions around the world. Immunocontraception is a promising approach; thus the present study examined the suitability of the widely used pig zona pellucida proteins (pZP) for contraception in feral domestic cats. Purified zona pellucida proteins obtained from pig and cat ovaries were used to produce highly specific antisera in rabbits. Antibodies against pZP raised in rabbits or lions were not effective inhibitors of either in vitro sperm binding (cat spermatozoa to cat oocytes) or in vitro fertilization in cats, whereas antibodies against feline zona pellucida proteins (fZP) raised in rabbits showed a dose-dependent inhibition of in vitro fertilization. Immunoelectrophoresis, ELISA and immunohistology of ovaries confirmed these results, showing crossreactivity of anti-fZP sera to fZP and to a lesser extent to pZP, but no interaction of anti-pZP sera with fZP. It is concluded that cat and pig zonae pellucidae express a very small number of shared antigenic determinants, making the use of pZP vaccine in cats questionable. A contraceptive vaccine based on feline zona pellucida determinants will be a better choice for the control of reproduction in feral cats if immunogenity can be achieved.

[Health status and causes of mortality in feral cats in a delimited area of the inner city of Berlin]. / Gesundheitsstatus und Mortalitätsursachen verwilderter Hauskatzen in einem Untersuchungsgebiet in Berlin-Mitte.

Results of the veterinary examination of feral cats living in a delimited area of Berlin city are presented. Between 1996 and 1999 thirty nine cats were investigated, among them eleven individuals twice. All animals were positive for one or several pathologies, but only seven cats were in bad condition. Most common were periodontal and gingival diseases, followed by conjunctivitis. Five cats were positive for FIV, seven for FeLV, one tomcat for both. Twenty six cats vanished during the study period of 42 months, only one third of cats survived and remained in the study area throughout. Four cats were given to pet lovers, nine cats disappeared without trace, seven animals died in traffic accidents and six cats died of illnesses. Cats less than three years of age vanished more often than expected from their representation in the population. Dirty or large feeding places for cats constitute a source of infections. Feeding sites should be accessible to only few individuals and left-overs that may attract stray cats, rats or birds should not remain at feeding places.

Dopamine and the regulation of cell proliferation in gerbil (Meriones unguiculatus) pyloric mucosa.

The epithelium of the digestive system mucosa consists of a highly dynamic cell population. The conditions under which mitotic activity in the gastrointestinal epithelium is regulated is as yet poorly understood. Nevertheless, it is assumed that some biogenic amines might be involved. Having demonstrated that dopaminergic cells occur in the stomach of gerbils (Meriones unguiculatus), in the present study we examined the influence of dopamine antagonist haloperidol on the proliferation of epithelial cells in the mucosa of the stomach. Proliferating cells were detected immunocytochemically and quantified after in-vivo labeling with 5-bromo-2'-desoxyuridine in both haloperidol- and saline-treated animals. The results show that acute doses of haloperidol significantly increases the proliferation rate in the pyloric mucosa, suggesting that dopamine plays a probable modulatory role in the regulation of mitotic activity. These findings are discussed with regard to the role of paraneurons in regulating epithelial mitosis.

Demonstration of dopamine immunoreactivity in open and closed type endocrine cells of gerbil (Meriones unguiculatus) stomach.

Dopamine-immunoreactive cells were identified in the stomach of gerbils using a selective antibody against glutaraldehyde-conjugated dopamine. In the pyloric area dopamine-containing cells were exclusively localized in the basal part of the mucous membrane, whereas in the fundic area dopaminergic cells were seen throughout the basodistal extent of the mucous membrane. Dopamine-containing cells belong to the class of closed and open type endocrine cells and were found in the fundic area and in the pyloric area respectively. These findings are discussed along with the likely modulatory function of dopamine in peripheral tissues.