Tumor-agnostic plasma assay for circulating tumor DNA detects minimal residual disease and predicts outcome in locally advanced squamous cell carcinoma of the head and neck.

BACKGROUND: Forty to fifty percent of patients with locally advanced squamous cell carcinoma of the head and neck (LA SCCHN) relapse despite multimodal treatment. Circulating tumor DNA (ctDNA) has the potential to detect minimal residual disease (MRD) after curative-intent therapy and to identify earlier which patients will progress. We developed a tumor-agnostic plasma ctDNA assay to detect MRD in unselected LA SCCHN with the aim of predicting progression-free survival (PFS) and overall survival without the need for tumor sequencing. PATIENTS AND METHODS: A 26-gene next-generation sequencing panel was constructed that included the most frequently mutated genes in SCCHN and two HPV-16 genes. MRD was assessed in each patient through an in-house informatic workflow informed by somatic mutations identified in the corresponding pre-treatment plasma sample. The presence of MRD was defined as the detection of ctDNA in one plasma sample collected within 1-12 weeks of the end of curative treatment. The primary endpoint was the PFS rate at 2 years. At least 32 patients were planned for inclusion with the hypothesis that PFS at 2 years was >80% in MRD-negative patients and <30% in MRD-positive patients (α = 0.05, ß = 0.9). RESULTS: We sequenced DNA from 116 plasma samples derived from 53 LA SCCHN patients who underwent curative-intent treatment. ctDNA was detected in 41/53 (77%) patients in the pre-treatment samples. Out of these 41 patients, 17 (41%) were MRD positive after treatment. The 2-year PFS rate was 23.53% (9.9% to 55.4%) and 86.6% (73.4% to 100%) in MRD-positive and MRD-negative patients, respectively (P < 0.05). Median survival was 28.37 months (14.30 months-not estimable) for MRD-positive patients and was not reached for the MRD-negative cohort (P = 0.011). CONCLUSIONS: Our ctDNA assay detects MRD in LA SCCHN and predicts disease progression and survival without the need for tumor sequencing, making this approach easily applicable in daily practice.

Temporary threshold shift after noise exposure in hypobaric hypoxia at high altitude: results of the ADEMED expedition 2011.

OBJECTIVES: To evaluate whether there is an increased risk for noise-induced hearing loss at high altitude rsp. in hypobaric hypoxia. METHODS: Thirteen volunteers got standard audiometry at 125, 250, 500, 750, 1000, 1500, 2000, 3000, 4000, 6000, and 8000 Hz before and after 10 min of white noise at 90 dB. The system was calibrated for the respective altitude. Measurements were performed at Kathmandu (1400 m) and at Gorak Shep (5300 m) (Solo Khumbu/Nepal) after 10 days of acclimatization while on trek. Temporary threshold shift (TTS) was analyzed by descriptive statistics and by factor analysis. RESULTS: TTS is significantly more pronounced at high altitudes. Acclimatization does not provide any protection of the inner ear, although it increases arterial oxygen saturation. CONCLUSION: The thresholds beyond which noise protection is recommended (> 80 dB) or necessary (> 85 dB) are not sufficient at high altitudes. We suggest providing protective devices above an altitude of 1500 m ("ear threshold altitude") when noise level is higher than 75 dB and using them definitively above 80 dB. This takes the individual reaction on hypobaric hypoxia at high altitude into account.

Hydrous mantle transition zone indicated by ringwoodite included within diamond.

The ultimate origin of water in the Earth's hydrosphere is in the deep Earth--the mantle. Theory and experiments have shown that although the water storage capacity of olivine-dominated shallow mantle is limited, the Earth's transition zone, at depths between 410 and 660 kilometres, could be a major repository for water, owing to the ability of the higher-pressure polymorphs of olivine--wadsleyite and ringwoodite--to host enough water to comprise up to around 2.5 per cent of their weight. A hydrous transition zone may have a key role in terrestrial magmatism and plate tectonics, yet despite experimental demonstration of the water-bearing capacity of these phases, geophysical probes such as electrical conductivity have provided conflicting results, and the issue of whether the transition zone contains abundant water remains highly controversial. Here we report X-ray diffraction, Raman and infrared spectroscopic data that provide, to our knowledge, the first evidence for the terrestrial occurrence of any higher-pressure polymorph of olivine: we find ringwoodite included in a diamond from Juína, Brazil. The water-rich nature of this inclusion, indicated by infrared absorption, along with the preservation of the ringwoodite, is direct evidence that, at least locally, the transition zone is hydrous, to about 1 weight per cent. The finding also indicates that some kimberlites must have their primary sources in this deep mantle region.

Activity and safety of afatinib in a window preoperative EORTC study in patients with squamous cell carcinoma of the head and neck (SCCHN).

Background: To investigate the activity and safety of afatinib in the preoperative treatment of squamous cell carcinoma of the head and neck (SCCHN). Patients and methods: This study was an open-label, randomized, multicenter, phase II window of opportunity trial. Treatment-naïve SCCHN patients selected for primary curative surgery were randomized (5 : 1 ratio) to receive afatinib during 14 days (day -15 until day -1) before surgery (day 0) or no treatment. Tumor biopsies, 2-[fluorine-18]-fluoro-2-deoxy-d-glucose positron emission tomography (FDG-PET), and magnetic resonance imaging (MRI) were carried out at diagnosis and just before surgery. The primary end point was metabolic FDG-PET response (according to EORTC guidelines). Other end points included response assessment based on the Response Evaluation Criteria In Solid Tumors (RECIST) v1.1, dynamic contrast-enhanced (DCE)-MRI, diffusion weighted (DW)-MRI, safety, and translational research (TR). Results: Thirty patients were randomized: 25 to afatinib and 5 to control arm. Of the 23 eligible patients randomized to afatinib, 16 (70%; 95% CI: 47% to 87%) patients had a partial metabolic FDG-PET response (PMR). Five patients (22%; 95% CI: 8% to 44%) showed a partial response by RECISTv1.1. Responses assessed via DCE-MRI and DWI-MRI did not show a strong association with PMR or RECIST. One patient discontinued afatinib after 11 days for grade 3 diarrhea with subsequent renal failure and 24 days delay in surgery. No grade 4 toxicities or surgical comorbidities related to afatinib were reported. TR results indicated that PMR was more frequent in the tumors with high Cluster3-hypoxia score expression and with TP53 wild type. Conclusion: Afatinib given for 2 weeks to newly diagnosed SCCHN patients induces a high rate of FDG-PET partial metabolic response and partial response according to RECISTv1.1. Afatinib can be safely administered before surgery. Although exploratory, the hypoxic gene signature needs further investigations as a predictive biomarker of afatinib activity. Clinical trial registration: ClinicalTrials.gov: NCT01538381.

Differentiation of healthy and malignant tissue in colon cancer patients using optical spectroscopy: A tool for image-guided surgery.

BACKGROUND: Surgery for colorectal cancer aims for complete tumor resection. Optical-based techniques can identify tumor and surrounding tissue through the tissue specific optical properties, absorption and scattering, which are both influenced by the biochemical and morphological composition of the tissue. OBJECTIVE: To evaluate the feasibility of dual-modality Diffuse Reflectance Spectroscopy-Fluorescence Spectroscopy (DRS-FS) for discrimination between healthy and malignant tissue in colorectal surgery. METHODS: Surgical specimens from colorectal cancer patients were measured immediately after resection using a fiber-optic needle capable of dual-modality DRS-FS. Model-based analyses were used to derive scattering and absorption coefficients and intrinsic fluorescence. Volume fractions of chromophores were estimated. Furthermore, optical data were recorded along a trajectory from healthy tissue towards tumor. RESULTS: Spectral characteristics were identified in 1,273 measured spectra from 21 specimens. Combined DRS and FS discriminated tumor from surrounding tissue with a sensitivity of 95% and a specificity of 88%. Significant spectral changes were seen along the trajectory from healthy tissue to tumor. CONCLUSION: This study demonstrates that dual-modality DRS-FS can identify colorectal cancer from surrounding healthy tissue. The quantification of comprehensible parameters allows robust classification and facilitates extrapolation towards the clinical setting. The technique, here demonstrated in a needle like probe, can be incorporated into surgical tools for optically guided surgery in the near future. Lasers Surg. Med. 47:559-565, 2015. © 2015 Wiley Periodicals, Inc.

[Turnover of Non-medical Staff in Outpatient Oncology Practices: Is Building Social Capital a Solution?]. / Fluktuation bei nicht-ärztlichem Personal in onkologischen Schwerpunktpraxen: Sozialkapitalaufbau als Lösungsansatz?

STUDY AIM: While a lot is known about potential and actual turnover of non-medical hospital staff, only few data exist for the outpatient setting. In addition, little is known about actual instruments which leaders can use to influence staff turnover in physician practices. In the literature, the social capital of an organisation, which means the amount of trust, common values and reciprocal behaviour in the organisation, has been discussed as a possible field of action. In the present study, staff turnover as perceived by outpatient haematologists and oncologists is presented and analysed as to whether social capital is associated with that staff turnover. In conclusion, measures to increase the social capital of a practice are presented. METHODS: The present study is based on data gathered in a questionnaire-based survey with members of the Professional Organisation of -Office-Based Haematologists and Oncologists (N=551). The social capital of the practice was captured from the haematologists and oncologists using an existing and validated scale. To analyse the impact of the practice's social capital on staff turnover, as perceived by the physicians, bivariate correlations and linear regression analyses were calculated. RESULTS: In total, 152 haematologists and oncologists participated in the study which represents a response rate of 28%. In the regression analyses, social capital appears as a significant and strong predictor of staff turnover (beta=-0.34; p<0.001). CONCLUSIONS: Building social capital within the practice may be an important contribution to reducing staff turnover although the underlying study design does not allow for drawing causal conclusions regarding this relationship. To create social capital in their practice, outpatient physicians may apply measures that facilitate social interaction among staff, foster trust and facilitate cooperation. Such measures may already be applied when hiring and training new staff, but also continuously when leading employees and when organising work tasks, e.g., by establishing regular team meetings.

Stimulation of duodenal biopsies and whole blood from dogs with food-responsive chronic enteropathy and healthy dogs with Toll-like receptor ligands and probiotic Enterococcus faecium.

The composition of the microbiome plays a significant role in the pathogenesis of inflammatory bowel disease (IBD) in humans and chronic enteropathies (CE) in dogs. The administration of probiotic micro-organisms is one way of modulating the microbiome, but experiments elucidating mechanisms of action of probiotics in the intestine of healthy and CE dogs are lacking. The aim of our study was to investigate the effects of different Toll-like receptor (TLR) ligands and Enterococcus faecium (EF) on ex vivo cultured duodenal samples and whole blood (WB) from dogs with food-responsive chronic enteropathy (FRE) when compared to healthy dogs. Biopsy stimulation was performed in 17 FRE and 11 healthy dogs; WB stimulation was performed in 16 FRE and 16 healthy dogs. Expression of TLR2, 4, 5 and 9, IL-17A, IL-22, IFNy, TNFα, IL-4, IL-10, TGFß and PPARy was determined in biopsies by quantitative polymerase chain reaction (PCR). In addition, production of TNFα, IL-10, IFNy and IL-17A protein in WB and biopsy supernatants was assessed by ELISA. Treatment with individual TLR ligands or EF induced a variety of changes in the expression of different TLRs and cytokines, but not necessarily a consistent change with a single stimulating agent. Even though cytokine protein could not be detected in supernatants from ex vivo stimulated biopsies, we found TNFα protein responses in blood to be opposite of the transcriptional responses seen in the biopsies. Stimulation of canine duodenal biopsies with TLR ligands can potentially induce anti-inflammatory gene expression, especially in healthy tissue, whereas the effects of EF were limited.

Can a stressed oncologist be good in a consultation? A qualitative study on the oncologists' perception.

The aim of this exploratory study was to examine how the working conditions and job stress of private practice oncologists (PPOs) affect their interaction with patients. Data for the study were collected through semi-structured interviews with PPOs selected based on purposeful sampling criteria. The data were evaluated using content analysis. Factors perceived by PPOs to influence their level of stress and patient care were some of their own personal characteristics as well as working conditions both within and outside their practices. Apart from being able to name specific stressors (e.g., dysfunctional organisational workflow and interruptions during medical encounters), the oncologists also mentioned individual and organisational resources (e.g., professional experience, well-educated nurses and good work organisation) for coping with job stress and improving interaction with patients. Within this study, we identified some obstacles on the individual and organisational level for good patient care, as working conditions which might lead to time pressure and stress, which subsequently have an impact on quality in patient care (e.g., less time for personal issues during patient consultations). Future stress research should conduct a more in-depth investigation of these and other interventions at both the individual and organisational levels in order to improve patient care.

An innovative approach to tracheotomy in patients with major obstruction of the upper airway.

BACKGROUND: Patients with severe dyspnea consecutive to locally advanced obstructive head and neck squamous cell carcinoma (HNSCC) or subglottic stenosis requiring definitive or temporary tracheotomy are frequently difficult to ventilate and intubate. MATERIALS AND METHODS: We describe a new procedure to perform tracheotomy easily and safely in patients with major obstruction of the upper airway. A catheter, specifically designed for cricothyroidotomy, was inserted into the trachea under local anesthesia. Then, general anesthesia was induced and the catheter was used as a guide for dilatation tracheotomy. From November 2009 to March 2013, the procedure was successfully used in 13 consecutive patients. Twelve out of 13 patients presented severe inspiratory dyspnea and stridor. RESULTS: During and after the procedure, no complications were reported. CONCLUSIONS: The reported technique is quickly performed and is a safe way to ensure short and long time ventilation of patients with major obstruction of the upper airway.

Primary undifferentiated carcinoma of the trachea.

BACKGROUND: Primary undifferentiated or lymphoepithelial carcinoma mainly occurs in the nasopharynx. Tracheal localization is exceedingly rare. To the best of our knowledge, only four cases have been reported previously, all in Asian patients. CASE REPORT: A 61-year-old male European patient presented with hemoptysis and cough for several months. The workup revealed a primary tracheal tumor without regional or distant metastasis. The patient was treated with tracheal resection followed by end-to-end reconstruction. Pathologic analysis of the tumor, including immunohistochemistry, confirmed the diagnosis of lymphoepithelioma-like carcinoma. Testing for Epstein-Barr virus by hybridization in situ was massively positive. With a follow-up at 15 months, the patient is alive and free of disease. CONCLUSION: We report the first case of lymphoepithelioma-like carcinoma in the trachea in the European population. Treatment possibilities are discussed. They should be based on each patient's clinical presentation and the results of their preoperative workup.

Efficacy and tolerance of oral versus parenteral cyanocobalamin supplement in hypocobalaminaemic dogs with chronic enteropathy: a controlled randomised open-label trial.

OBJECTIVES: Determine comparative tolerance of daily oral and weekly parenteral cobalamin supplementation, in hypocobalaminaemic dogs with chronic enteropathy. Determine whether oral is as effective as parenteral supplementation at achieving eucobalaminaemia, in hypocobalaminaemic dogs with protein-losing enteropathy, severe hypocobalaminaemia or high canine inflammatory bowel disease activity index at inclusion. MATERIALS AND METHODS: Thirty-seven client-owned dogs with hypocobalaminaemia and clinical signs of chronic enteropathy were prospectively enrolled in three UK referral centres. Dogs were randomly allocated to daily oral for 12 weeks or weekly parenteral cobalamin supplementation for 6 weeks and one additional dose 4 weeks later. Serum cobalamin, body condition score, canine inflammatory bowel disease activity index and bodyweight were assessed at inclusion, weeks 7 and 13. Serum methylmalonic acid concentration was evaluated at inclusion and at week 13. Owners completed treatment adherence, palatability, tolerance and satisfaction questionnaires at week 13. RESULTS: Nineteen dogs completed the study. All dogs orally supplemented achieved normal or increased cobalaminaemia at weeks 7 and 13. There was no statistical difference in cobalamin concentration at week 13 in dogs treated with oral or parenteral supplementation, regardless of presence of protein-losing enteropathy, severity of hypocobalaminaemia or canine inflammatory bowel disease activity index at inclusion. Serum methylmalonic acid concentration was not significantly different between oral and parenteral groups, neither were treatment adherence, satisfaction, and tolerance scores at week 13. CLINICAL SIGNIFICANCE: Oral is as effective and as well-tolerated as parenteral cobalamin supplementation in hypocobalaminaemic dogs with chronic enteropathy and severe clinical or biochemical phenotypes, and should be considered as a suitable treatment option regardless of disease severity.

Tumour response and safety of cetuximab in a window pre-operative study in patients with squamous cell carcinoma of the head and neck.

BACKGROUND: To investigate the safety and activity of cetuximab in the pre-operative treatment of squamous cell carcinoma of the head and neck (SCCHN). PATIENTS AND METHODS: Cetuximab was administered for 2 weeks before surgery to 33 treatment-naïve patients selected for primary surgical treatment. Tumour biopsies, 2-[fluorine-18]-fluoro-2-deoxy-d-glucose positron emission tomography ((18)FDG-PET) and imaging were carried out at baseline and before surgery. The primary aim of the study was safety and the secondary aims included metabolical, radiological and pathological tumour response. Five untreated patients were included as controls. RESULTS: Cetuximab given 24 h before surgery was safe. Ninety percent of patients had (18)FDG-PET partial response (EORTC guideline) in the cetuximab group versus 0% in the control group. Delta maximal standardized uptake values (ΔSUVmax) were correlated with tumour cellularity on the surgical specimens (P < 0.0001). For patients with ΔSUVmax less than -25% or less than -50%, Ki67 was significantly decreased by cetuximab (P = 0.01 and 0.003). Cetuximab induced down-regulation of pEGFR (P = 0.0004) and pERK (P = 0.003). CONCLUSIONS: Short-course pre-operative administration of cetuximab is safe and shows a high rate of (18)FDG-PET response. (18)FDG-PET response was correlated with residual tumour cellularity suggesting that (18)FDG-PET deserves further investigation as a potential early marker of cetuximab activity in SCCHN.

Biogeographical patterns and determinants of invasion by forest pathogens in Europe.

A large database of invasive forest pathogens (IFPs) was developed to investigate the patterns and determinants of invasion in Europe. Detailed taxonomic and biological information on the invasive species was combined with country-specific data on land use, climate, and the time since invasion to identify the determinants of invasiveness, and to differentiate the class of environments which share territorial and climate features associated with a susceptibility to invasion. IFPs increased exponentially in the last four decades. Until 1919, IFPs already present moved across Europe. Then, new IFPs were introduced mainly from North America, and recently from Asia. Hybrid pathogens also appeared. Countries with a wider range of environments, higher human impact or international trade hosted more IFPs. Rainfall influenced the diffusion rates. Environmental conditions of the new and original ranges and systematic and ecological attributes affected invasiveness. Further spread of established IFPs is expected in countries that have experienced commercial isolation in the recent past. Densely populated countries with high environmental diversity may be the weakest links in attempts to prevent new arrivals. Tight coordination of actions against new arrivals is needed. Eradication seems impossible, and prevention seems the only reliable measure, although this will be difficult in the face of global mobility.

Pitfalls in preoperative work-up of parotid gland tumours: 10-year series.

PROBLEMS/OBJECTIVES: Preoperative fine-needle aspiration cytology (FNAC) and magnetic resonance imaging (MRI) are the two most widely accepted diagnostic techniques used for the assessment of parotid gland tumours. We retrospectively evaluated the ability of FNAC and MRI to predict malignancy in parotid gland tumours. METHODOLOGY: Over a period of 10 years (2002-2011), parotidectomy for primary parotid gland tumours was performed in a consecutive series of 178 patients. Preoperative MRI was performed in 75% (133/178) of cases, and preoperative FNAC was performed in 70% of cases (124/178). Both modalities were applied in 53% (94/178) of patients. Sensitivity, specificity, and accuracy were analyzed retrospectively for each subgroup of patients. RESULTS: The sensitivity, specificity, and accuracy for predicting malignancy were 45%, 89%, and 84%, respectively, for FNAC (including only diagnostic cytology), and 40%, 88%, and 81%, respectively, for MRI. In the subgroup of patients who underwent both MRI and FNAC, sensitivity, specificity, and accuracy were 50%, 85%, and 80%, respectively. Preoperative MRI values improved significantly after introduction of diffusion-weighted (DW) acquisition in 2007 (71%, 93%, and 91%, respectively). CONCLUSIONS: Compared to previously published results, the high number of nondiagnostic smears and the low sensitivity rates in our series were disappointing, In part, this can be explained by the low percentage of malignant tumours and the high number of low-grade tumours among these. We discuss possibilities for improving preoperative performance, such as ultrasound-guided FNAC.

Incidence and presentation of new-onset type 1 diabetes in children and adolescents from Germany during the COVID-19 pandemic 2020 and 2021: Current data from the DPV Registry.

AIMS: To determine whether the incidence of type 1 diabetes mellitus (T1D), autoantibody-negative diabetes, and diabetic ketoacidosis (DKA) at diabetes onset in 2020 and 2021 changed when compared to long-standing trends. METHODS: Our study is based on diabetes manifestation data of the 0.5-<18-year-old children/adolescents from the German multicenter Diabetes Prospective Follow-up Registry. Based on long-term pre-pandemic trends from 2011 to 2019, we estimated adjusted incidence rate ratios (IRR) for T1D and DKA, and prevalence rate ratios (PRR) regarding autoantibody status with 95 % confidence intervals (CI) for the years 2020 and 2021 (observed versus predicted rates), using multivariable negative binomial or beta-binomial regression, respectively. RESULTS: We analyzed data of 30,840 children and adolescents with new-onset T1D. The observed incidences were significantly higher than the predicted incidences (IRR2020 1.13 [1.08-1.19]; IRR2021 1.20 [1.15-1.26]). The prevalence of autoantibody-negative diabetes did not change (PRR2020 0.91 [0.75-1.10]; PRR2021 1.03 [0.86-1.24]). The incidence of DKA during the pandemic was higher than predicted (IRR2020 1.34 [1.23-1.46]; IRR2021 1.37 [1.26-1.49]). CONCLUSIONS: An increase in the incidences of T1D and DKA, but not of autoantibody-negative diabetes was observed during both pandemic years. Further monitoring and efforts for DKA prevention at onset are necessary.

Phase II study of figitumumab in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck: clinical activity and molecular response (GORTEC 2008-02).

BACKGROUND: Preclinical studies suggest that insulin-like growth factor-1 receptor (IGF-1R) blockage could be a promising therapeutic target in squamous cell carcinoma of the head and neck (SCCHN). Therefore, we investigated the efficacy and toxicity of figitumumab, an anti-IGF-1R monoclonal antibody, in palliative SCCHN. PATIENTS AND METHODS: Patients with palliative SCCHN progressing after platinum-based therapy were treated with figitumumab i.v. 20 mg/kg, every 3 weeks. The primary end point was the disease control rate at 6-8 weeks after treatment initiation. Tumor biopsies and plasma samples were collected before and after figitumumab administration to monitor the molecular response. RESULTS: Seventeen patients were included. Only two patients achieved stable disease at 6-8 weeks. Median overall survival and progression-free survival were 63 and 52 days, respectively. The main grade 3-4 adverse event was hyperglycemia (41%). Translational research showed that figitumumab downregulated IGF-1R at the surface of tumor cells with activation of the epidermal growth factor receptor (EGFR) pathway, as shown by the upregulation of p-EGFR in tumor cells (P=0.016), and an increase in the plasma level of tumor growth factor-alpha (P=0.006). CONCLUSION: Figitumumab monotherapy has no clinically significant activity in unselected palliative SCCHN.

Bile duct injury and use of cholangiography during laparoscopic cholecystectomy.

BACKGROUND: Bile duct injury (BDI) remains the most serious complication of laparoscopic cholecystectomy (LC). A Swiss database was used to identify risk factors for BDI and to assess the effect of intraoperative cholangiography (IOC). METHODS: Data for patients from 114 Swiss institutions who underwent LC for acute or chronic cholecystitis between 1995 and 2005 were used in univariable and logistic regression analyses. RESULTS: In total 31 838 patients, mean(s.d.) age 54·4(15·9) years, were analysed. The incidence of BDI was 0·3 per cent (101 patients), which did not change over time (P = 0·560). Univariable analysis revealed that male patients had a higher risk of BDI (0·5 per cent versus 0·2 per cent in female patients; P = 0·001), as did patients whose operation lasted at least 150 min (1·1 per cent versus 0·1 per cent for operating time of less than 150 min; P < 0·001). Logistic regression confirmed male sex (odds ratio (OR) 1·89, 95 per cent confidence interval 1·27 to 2·81) and prolonged surgery (OR 12·60, 10·87 to 23·81) as independent risk factors. Comparison of groups with and without intraoperative cholangiography showed no difference in the incidence of BDI (both 0·3 per cent; P = 0·755) and BDIs missed during surgery (10 versus 8 per cent; P = 0·737). CONCLUSION: Male sex and prolonged laparoscopic surgery are independent risk factors for BDI during LC. Frequent use of IOC does not seem to reduce BDI or the number of injuries missed during surgery.

[Calciphylaxis. A call for interdisciplinary cooperation]. / Kalziphylaxie. Eine nephrologisch-dermatologische Herausforderung.

Calciphylaxis is a rare, often very painful and potentially life-threatening disorder at the interface between nephrology and dermatology. It is characterized by skin lesions and ulcerations following calcification and occlusion of cutaneous arterioles. Most patients have chronic kidney disease or are on dialysis. A concert of various, still incompletely understood local and systemic risk factors is necessary to cause the development of calciphylaxis. Since randomized prospective trials are missing, interdisciplinary treatment is based on pathophysiological considerations as well as evidence derived from case reports or case series. Normalization of mineral metabolism, intensifying dialysis and avoidance of coumarins, as well as administration of calcimimetics, bisphosphonates and sodium thiosulfate and hyperbaric oxygen therapy are often used. Supportive measures include analgesics, antibiotics and local wound care. We have initiated an internet-based registry for patients with calciphylaxis in order to collect data for improved patient care (with support from Amgen) (www.calciphylaxie.de).

Observer accuracy in the detection of pulmonary nodules on CT: effect of cine frame rate.

AIM: To assess the effect of cine frame rate on the accuracy of the detection of pulmonary nodules at computed tomography (CT). MATERIALS AND METHODS: CT images of 15 consecutive patients with (n = 13) or without (n = 2) pulmonary metastases were identified. Initial assessment by two thoracic radiologists provided the "actual" or reference reading. Subsequently, 10 radiologists [board certified radiologists (n = 4) or radiology residents (n = 6)] used different fixed cine frame rates for nodule detection. Within-subjects analysis of variance (ANOVA) was used to evaluate the data. RESULTS: Eighty-nine nodules were identified by the thoracic radiologists (median 8, range 0-29 per patient; median diameter 9 mm, range 4-40 mm). There was a non-statistically significant trend to reduced accuracy at higher frame rates (p=0.113) with no statistically significant difference between experienced observers and residents (p = 0.79). CONCLUSION: The accuracy of pulmonary nodule detection at higher cine frame rates is reduced, unrelated to observer experience.

Solid phase gastric emptying times in the dog measured by 13C-sodium-acetate breath test and 99mTechnetium radioscintigraphy.

OBJECTIVE: The aim of the study was to assess solid gastric emptying via non-invasive 13C-sodium acetate breath test and compare this technique to 99mTechnetium scintigraphy in 12 healthy adult dogs. MATERIAL AND METHODS: The dogs were fed a test meal containing either 100mg 13C-sodium acetate or 150-250 MBq 99mTechnetium albumin colloid. Breath test and scintigraphy were performed on two consecutive days; this set of procedures was repeated in all dogs. Breath samples and scintigrams were obtained at baseline and every 15minutes for 4 hours, then every 30 minutes for another 2 hours. 25%, 50% and 75% gastric emptying times for breath test (Gt25%b, Gt50%b, Gt75%b) and scintigraphy (Gt25%s, Gt50%s, Gt75%s) were calculated and compared. RESULTS: The mean (±SD) Gt50%b and Gt50%s were 165 (±28.1) and 71 (±16.6)minutes, respectively. There was a significant correlation at all three gastric emptying times between breath test and scintigraphy. Conclusion and clinical significance: While gastric emptying times between both methods varied considerably, both methods correlated significantly showing that the gastric emptying breath test can be used to assess gastric emptying times in dogs.