Robot-assisted minimally invasive thoraco-laparoscopic esophagectomy versus minimally invasive esophagectomy for resectable esophageal adenocarcinoma, a randomized controlled trial (ROBOT-2 trial).

BACKGROUND: For patients with esophageal adenocarcinoma or cancer of the gastroesophageal junction, radical esophagectomy with 2-field lymphadenectomy is the cornerstone of the multimodality treatment with curative intent. Both conventional minimally invasive esophagectomy (MIE) and robot assisted minimally invasive esophagectomy (RAMIE) were shown to be superior compared to open transthoracic esophagectomy considering postoperative complications. However, no randomized comparison exists between MIE and RAMIE in the Western World for patients with esophageal adenocarcinoma. METHODS: This is an investigator-initiated and investigator-driven multicenter randomized controlled parallel-group superiority trial. All adult patients (age ≥ 18 and ≤ 90 years) with histologically proven, surgically resectable (cT1-4a, N0-3, M0) esophageal adenocarcinoma of the intrathoracic esophagus or adenocarcinoma of the gastroesophageal junction and with European Clinical Oncology Group performance status 0, 1 or 2 will be assessed for eligibility and included after obtaining informed consent. Patients (n = 218) with resectable esophageal adenocarcinoma of the intrathoracic esophagus or adenocarcinoma of the gastroesophageal junction are randomized to either RAMIE (n = 109) or MIE (n = 109). The primary outcome of this study is the total number of resected abdominal and mediastinal lymph nodes specified per lymph node station. CONCLUSION: This is the first randomized controlled trial designed to compare RAMIE to MIE as surgical treatment for resectable esophageal adenocarcinoma or adenocarcinoma of the gastroesophageal junction in the Western World. The hypothesis of the proposed study is that RAMIE will result in a higher abdominal and mediastinal lymph node yield specified per station compared to conventional MIE. Short-term results and the primary endpoint (total number of resected abdominal and mediastinal lymph nodes per lymph node station) will be analyzed and published after discharge of the last randomized patient within this trial. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04306458 . Registered 13th March 2020, https://clinicaltrials.gov/ct2/show/NCT04306458; Date of first enrolment 18.01.2021; Target sample size 218; Recruitment status: Recruiting; Protocol version 2; Issue date 10.03.2020; Rev. 02.02.2021; Authors ET, PCvdS, PPG.

EndoPredict® in early hormone receptor-positive, HER2-negative breast cancer.

PURPOSE: Evaluating consecutive early breast cancer patients, we analyzed both the impact of EndoPredict® on clinical decisions as well as clinico-pathological factors influencing the decision to perform this gene expression test. METHODS: Hormone receptor (HR)-positive and human epidermal growth factor receptor 2 (HER2)-negative early breast cancer patients treated between 2011 and 2016 were included in this study to investigate the role of EndoPredict® (EPclin) in the treatment of early breast cancer. A main study aim was to analyze the changes in therapy recommendations with and without EPclin. In addition, the impact of clinico-pathological parameters for the decision to perform EPclin was examined by Pearson's chi-squared test (χ2-test) and Fisher's exact test as well as univariate and multivariate logistic regressions. RESULTS: In a cohort of 869 consecutive early HR-positive, HER-negative breast cancer patients, EPclin was utilized in 156 (18.0%) patients. EPclin led to changes in therapy recommendations in 33.3% (n = 52), with both therapy escalation in 19.2% (n = 30) and de-escalation in 14.1% (n = 22). The clinico-pathological factors influencing the use of EPclin were age (P < 0.001, odds ratio [OR] 0.498), tumor size (P = 0.011, OR 0.071), nodal status (P = 0.021, OR 1.674), histological grade (P = 0.043, OR 0.432), and Ki-67 (P < 0.001, OR 3.599). CONCLUSIONS: EPclin led to a change in therapy recommendations in one third of the patients. Clinico-pathological parameters such as younger age, smaller tumor size, positive nodal status, intermediate histological grade and intermediate Ki-67 had a significant influence on the use of EndoPredict®.

Unilateral vestibular schwannoma and meningiomas in a patient with PIK3CA-related segmental overgrowth: Co-occurrence of mosaicism for 2 rare disorders.

A 28-year-old female with PIK3CA-related segmental overgrowth presented with headaches. She also had a unilateral vestibular schwannoma (VS), as well as 3 small (<2 cm) meningiomas, which according to the Manchester consensus diagnostic criteria for neurofibromatosis 2 (NF2) is sufficient for a clinical diagnosis. Analysis of blood revealed a mosaic PIK3CA c.2740G>A (p.Gly914Arg) mutation, confirming the diagnosis of PIK3CA-related overgrowth, but no mutations in NF2 were detected. Although VS has not previously been reported in PIK3CA-related segmental overgrowth, meningiomas have, raising the question of whether this patient's VS and meningiomas represent coincidental NF2 or phenotypic extension of her overgrowth syndrome. Genetic analysis of the VS revealed a heterozygous NF2 mutation c.784C>T (p.Arg262Ter) and loss of a portion of 22q, including NF2, SMARCB1, and LZTR1 genes. These results suggest that the patient has 2 different mosaic disorders, NF2 and PIK3CA-related overgrowth. The PIK3CA mutation was also present in the VS. Confirmation of the clinical diagnosis of mosaic NF2 in this patient has implications for monitoring and highlights the possibility of co-occurrence of mosaicism for multiple rare disorders in a single patient.

Structured assessment of laparoscopic camera navigation skills: the SALAS score.

BACKGROUND: Tools are needed to assess laparoscopic camera navigation (LCN) in the operating room. Here, we aimed to develop an objective rating scale for LCN. STUDY DESIGN: We defined the following key aspects of LCN: operational field centering, correct angle of the horizon, correct instrument visualization, verbal commands from the operating surgeon, and manual corrections from the operating surgeon. We then developed a score based on intraoperative error evaluation from intraoperative recordings of 80 procedures. Finally, the newly developed score was validated by four different raters using video-based analysis of 20 elective laparoscopic cholecystectomies. RESULTS: We developed and validated a tool for the structured assessment of laparoscopic assistant skills (SALAS). This score showed good internal consistency, with a Cronbach's alpha of > 0.7. Intraclass correlation revealed a low interrater variability (ICC 0.866) for the total score. Comparison of experienced and inexperienced camera assistants revealed significantly better SALAS scores for experienced assistants (p < 0.05). CONCLUSION: Our present results show that SALAS score is valid, reliable, and practicable. This score can be used for future investigations of camera navigation efficiency and training.

[Effect of different training methods on the use of the i-gel laryngeal mask by lay persons on a manikin]. / Auswirkung verschiedener Ausbildungsmethoden auf die Anwendung der i-gel®-Larynxmaske durch Laien am Phantom.

BACKGROUND: Several studies have described the successful application of extraglottic airways by lay people to a phantom. OBJECTIVES: This study examined the influence of the training method on the success of the application. METHODS: A total of 150 visitors of a shopping mall were asked to place an i­gel laryngeal mask (Intersurgical GmbH, Sankt Augustin, Germany) on a manikin. The short instruction was randomized and performed either as a practical demonstration or through the self-study of an illustrated manual. RESULTS: Application success in the first attempt was 95.8 % for the practical demonstration group and 78.5 % for the written instruction group (p = 0.001). Placement times were also significantly different (median 11.5 s vs. 22.5 s, p < 0.001). CONCLUSIONS: Learning success can be achieved with both training methods. Initially, a hands-on training should be carried out with a practical demonstration.

Effect of intraoperative nerve monitoring on postoperative vocal cord palsy rates after thyroidectomy: European multicentre registry-based study.

BACKGROUND: Intraoperative nerve monitoring (IONM) of the recurrent laryngeal nerve (RLN) predicts the risk of vocal cord palsy (VCP). IONM can be used to adapt the surgical strategy in order to prevent bilateral VCP and associated morbidity. Controversial results have been reported in the literature for the effect of IONM on rates of VCP, and large multicentre studies are required for elucidation. METHODS: Patients undergoing first-time thyroidectomy for benign thyroid disease between May 2015 and January 2019, documented prospectively in the European registry EUROCRINE®, were included in a cohort study. The influence of IONM and other factors on the development of postoperative VCP was analysed using multivariable regression analysis. RESULTS: Of 4598 operations from 82 hospitals, 3542 (77·0 per cent) were performed in female patients. IONM was used in 4182 (91·0 per cent) of 4598 operations, independent of hospital volume. Postoperative VCP was diagnosed in 50 (1·1 per cent) of the 4598 patients. The use of IONM was associated with a lower risk of postoperative VCP in multivariable analysis (odds ratio (OR) 0·34, 95 per cent c.i. 0·16 to 0·73). Damage to the RLN noted during surgery (OR 24·77, 12·91 to 48·07) and thyroiditis (OR 2·03, 1·10 to 3·76) were associated with an increased risk of VCP. Higher hospital volume correlated with a lower rate of VCP (OR 0·05, 0·01 to 0·13). CONCLUSION: Use of IONM was associated with a low rate of postoperative VCP.

ANTECEDENTES: La monitorización nerviosa intraoperatoria (intraoperative nerve monitoring, IONM) del nervio laríngeo recurrente (recurrent laryngeal nerve, RLN) predice el riesgo de parálisis de la cuerda vocal (vocal cord palsy, VCP). La IONM se puede utilizar para adaptar la estrategia quirúrgica con el objetivo de prevenir la VCP bilateral y la morbilidad asociada. La literatura describe resultados controvertidos de la influencia de la IONM sobre las tasas de VCP, por lo que se requieren grandes estudios multicéntricos para aclararlo. MÉTODOS: De mayo de 2015 a enero de 2019, las tiroidectomías efectuadas como primera intervención quirúrgica por patología tiroidea benigna - documentadas prospectivamente en el registro europeo EUROCRINE© - se incluyeron en un estudio de cohortes. La influencia de la IONM y otros factores sobre el desarrollo de VCP postoperatoria fueron analizados utilizando un análisis de regresión multivariable. RESULTADOS: De 4.598 operaciones efectuadas en 82 hospitales e incluidas en el estudio, 3.542 (77,0%) fueron realizadas en mujeres. La IONM se utilizó en 4.182 de 4.598 (91,0%) operaciones independientemente del volumen del hospital. La VCP postoperatoria se diagnosticó en 50 de 4.598 (1,1%) pacientes. La utilización de IONM se asoció con un menor riesgo de VCP postoperatoria en el análisis multivariable (razón de oportunidades, odds ratio, OR 0,34 (i.c. del 95% 0,16-0,73)). La detección de lesión del RLN durante la cirugía (OR 24,77 (12,91 a 48,07)) y la tiroiditis (OR 2,03 (1,10 a 3,76)) se asociaron con un riesgo aumentado de VCP. Un elevado volumen de casos se correlacionó con menor frecuencia de VCP (OR 0,05 (0,01 a 0,13)). CONCLUSIÓN: La utilización de la IONM se asoció con una baja tasa de VCP postoperatoria.

Conversion coefficients for the estimation of effective doses in intraoral and panoramic dental radiology from dose-area product values.

Conversion coefficients for the estimation of effective doses in intraoral and panoramic dental radiology from dose-area product (DAP) values were determined by measuring organ-absorbed doses and the corresponding DAP values. Measurements were performed for all standard intraoral radiological projections and standard panoramic examination at different exposure parameters. Organ-absorbed doses were measured using thermoluminescent detectors and an adult anthropomorphic phantom specially designed for dosimetric study in dental radiology. Different techniques for the calculation of effective doses were evaluated. Conversion coefficients derived from this study range from 0.008 to 0.132 microSv mGy(-1) cm(-2) for intraoral radiography and 0.055 to 0.238 microSv mGy(-1) cm(-2) for panoramic radiography.

Dose-area product measurements in panoramic dental radiology.

In this study, dose-area product (DAP) measurements in panoramic dental radiology have been performed in Germany. The results obtained in this study were proposed as diagnostic reference levels (DRLs). A representative number of dental panoramic units, both with digital and conventional image receptors, have been chosen. Common statistical parameters such as mean, standard deviation and 3rd quartile have been calculated. For four different standard programmes, 'large adult', 'adult male', 'adult female' and 'child', the proposed DRLs are 101, 87, 84 and 75 mGy cm(2), respectively. No clear tendency to a generalised dose reduction from the transition to digital techniques has been observed. Effective doses have been calculated from E/DAP conversion factors published in literature. Even though these values differ by a factor of approximately 3, upper limits of 15.8-21.2 microSv for the four different exposure settings were derived from the data.

Radiation exposure and dose evaluation in intraoral dental radiology.

In this study, dose area product measurements have been performed to propose diagnostic reference levels (DRLs) in intraoral dental radiology. Measurements were carried out at 60 X-ray units for all types of intraoral examinations performed in clinical routine. The third quartile values calculated range from 26.2 to 87.0 mGy cm(2). The results showed that there exists a large difference between the patient exposures among different dental facilities. It was also observed that dentists working with faster film type or higher tube voltage are not always associated with lower exposure. The study demonstrated the necessity to have the DRLs laid out as guidelines in dental radiology.

Dose-area product measurements and determination of conversion coefficients for the estimation of effective dose in dental lateral cephalometric radiology.

A study has been carried out to propose diagnostic reference levels (DRLs) for lateral cephalometric radiology in Germany based on the dose-area product (DAP). DRLs were proposed separately for child and adult exposure settings which are 26.4 and 32.6 mGy cm2, respectively. Organ absorbed doses from lateral cephalometric radiology were also measured using thermoluminescence detectors (TLDs) and an adult anthropomorphic phantom specially design for dosimetric study in dental radiology. Effective doses were then calculated using three different techniques where the salivary gland and brain tissue were given different weighting factors. Conversion coefficients for estimating effective dose from DAP value derived in this study range from 0.042 to 0.149 microSv/mGy cm2.

Radiation exposure to children in intraoral dental radiology.

In this study, dose area product (DAP) measurements have been performed aiming at establishing diagnostic reference levels (DRLs) in paediatric intraoral dental radiology. Measurements were carried out at 52 X-ray units for all types of intraoral examinations performed in clinical routine. Not all X-ray units have pre-set child exposure settings with reduced exposure time or in some cases lower tube voltage. Child examinations are carried out using adult exposure settings at these units, which increases the DAP third quartile values by up to 50%. For example, third quartile values for periapical examination ranges from 14.4 to 40.9 mGy cm(2) for child settings and 20.6 to 48.8 mGy cm(2) when the adult settings are included. The results show that there exists a large difference between the patient exposures among different dental facilities. It was also observed that clinics working with faster film type or higher tube voltage are not always associated with lower exposure.

Transfer of a supernumerary chromosome between vegetatively incompatible biotypes of the fungus Colletotrichum gloeosporioides.

Two biotypes (A and B) of Colletotrichum gloeosporioides infect the tropical legumes Stylosanthes spp. in Australia. These biotypes are asexual and vegetatively incompatible. However, field isolates of biotype B carrying a supernumerary 2-Mb chromosome, thought to originate from biotype A, have been reported previously. We tested the hypothesis that the 2-Mb chromosome could be transferred from biotype A to biotype B under laboratory conditions. Selectable marker genes conferring resistance to hygromycin and phleomycin were introduced into isolates of biotypes A and B, respectively. A transformant of biotype A, with the hygromycin resistance gene integrated on the 2-Mb chromosome, was cocultivated with phleomycin-resistant transformants of biotype B. Double antibiotic-resistant colonies were obtained from conidia of these mixed cultures at a frequency of approximately 10(-7). Molecular analysis using RFLPs, RAPDs, and electrophoretic karyotypes showed that these colonies contained the 2-Mb chromosome in a biotype B genetic background. In contrast, no double antibiotic colonies developed from conidia obtained from mixed cultures of phleomycin-resistant transformants of biotype B with biotype A transformants carrying the hygromycin resistance gene integrated in chromosomes >2 Mb in size. The results demonstrated that the 2-Mb chromosome was selectively transferred from biotype A to biotype B. The horizontal transfer of specific chromosomes across vegetative incompatibility barriers may explain the origin of supernumerary chromosomes in fungi.

The ftsZ gene of Haloferax mediterranei: sequence, conserved gene order, and visualization of the FtsZ ring.

We sequenced the ftsZ gene region of the halophilic archaeon Haloferax mediterranei and mapped the transcription start sites for the ftsZ gene. The gene encoded a 363-amino-acid long FtsZ protein with a predicted molecular mass of 38 kDa and an isoelectric point of 4.2. A high level of similarity to the FtsZ protein of Haloferax volcanii was apparent, with 97 and 90% identity at the amino acid and nucleotide levels, respectively. Structural conservation at the protein level was shown by visualization of the FtsZ ring structure in H. mediterranei cells using an antiserum raised against FtsZ of H. volcanii. FtsZ rings were observed in cells in different stages of division, including cells with pleomorphic shapes and cells that appeared to be undergoing asymmetric division. Cells were also observed that displayed constriction-like invaginations in the absence of an FtsZ ring, indicating that morphological data are not sufficient to determine whether pleomorphic Haloferax cells are undergoing cell division. Both the upstream and downstream gene order in the ftsZ region was found to be conserved within the genus Haloferax. Furthermore, the downstream gene order, which includes the secE and nusG genes, is conserved in almost all euryarchaea sequenced to date. The secE and nusG genes are likely to be transcriptionally and translationally coupled in Haloferax, and this co-expression may have been a selective force that has contributed to keeping the gene cluster intact.

[An effect of chromatographic fraction ultrafiltrate of plasma on aggregation of blood platelets in patients with chronic uremia]. / Wplyw frakcji chromatograficznych ultrafiltratów osocza na agregacje krwinek plytkowych chorych na przewlekla mocznice.

Chromatographic separation of ultrafiltrates from uremic patients on Sephadex A25 has showed that medium molecular weight substances were prior to the dialysis contained in 2 peaks in 6 patients, and in a single peak in 14 patients. The same substances were contained only in one peak after dialysis. Substances contained in the first peak inhibited blood platelets aggregation produced by ADP. Dialysis decreased this inhibitory effect.

[Uremic middle molecules in chronic renal insufficiency]. / Zachowanie sie zwiazków o sredniej masie czasteczkowej w przewleklej niewydolnosci nerek.

In patients with chronic glomerulonephritis the level of uremic middle molecules was determined in relation to a degree of activity and a cause of disease. The increase of uremic middle molecules was connected with the degree of renal destruction.

[Effect of deferoxamine on erythropoiesis in patients hemodialyzed for chronic renal insufficiency treated with erythropoietin]. / Wplyw deferoksaminy na proces erytropoezy u chorych hemodializowanych z przewlekla niewydolnoscia nerek leczonych erytropoetyna.

The aim of the study was to evaluate the effect of deferoxamine therapy on erythropoiesis, aluminium concentration and iron metabolism in hemodialyzed patients with chronic renal insufficiency treated with human recombinant erythropoietin (Eprex, Cilag). 8 hemodialyzed patients (2 female and 6 male) in long-term programme with aluminium serum concentration over 160 micrograms/l were treated with deferoxamine (5 mg/kg b.m.) during the last hour of hemodialysis in slowly intravenous infusion since 1 months. During this treatment aluminium and iron serum concentrations, serum iron-binding capacity, transferrin and hematocrit were determined before and after 1 months of deferoxamine therapy. The significant decrease of aluminium serum concentration (p < 0.05) and increase of hematocrit (p < 0.01), iron (p < 0.05) and serum iron-binding capacity (p < 0.001) were determined. The results of performed analysis indicate that aluminium is able to inhibit erythropoiesis induced by erythropoietin. The improvement in erythropoiesis and iron metabolism after deferoxamine therapy was observed.

[Effects of L-carnitine on erythropoiesis and blood platelet aggregation in patients with chronic renal failure treated with hemodialysis]. / Wplyw l-karnityny na erytropoeze i agregacje plytek krwi u chorych hemodializowanych z przewlekla niewydolnoscia nerek.

The aim of the work has to assess the effects of L-carnitine therapy on erythropoiesis and whole blood platelet aggregation. The studies were performed in 28 patients divided into 3 groups: I-group was given erythropoietin, II-group was given erythropoietin and L-carnitine, III-group was given L-carnitine. After 22 month of the therapy a statistically significant rise in hematocrit was observed in group III, improvement in muscle strength, a rise in free and total carnitine concentration was found in group II and III. There were no significant changes in urea concentration, platelet count and iron metabolism. Whole blood platelet aggregation induced by ADP, collagen and ristocetin was impaired relative to healthy volunteers. After 2 month of L-carnitine treatment of significant rise in collagen induced platelet aggregation was observed in group II.

[Use of low-molecular weight heparin during hemodialysis]. / Zastosowanie heparyny drobnoczasteczkowej w dializoterapii.

Coagulation parameters--platelet aggregation, beta-thromboglobulin, fibrinopeptide A were analyzes in patients with final chronic renal insufficiency during haemodialysis after a low molecular weight heparin application. In the study was documented that standard heparin is able to induce platelet aggregation. A low molecular weight heparin is suggested as sefex, because no influence on platelet aggregation was determined.

[The influence of multiple dialyzer reuse on selected coagulation parameters]. / Wplyw wielokrotnej reutylizacji dializatorów na wybrane parametry ukladu krzepniecia.

The aim of the study was to follow effects of multiple dialyzer reuse on some coagulation parameters. In a random group of 10 patients undergoing intermittent hemodialysis treatment, platelet coagulant, fibrinogen, BTG and PF4 concentrations were determined after 1st dialyzer usage and after 2 consecutive dialysis sessions after which the dialyzer was reused by manual method with 1% Dialyne solution. An increase in fibrinogen concentration after 240 min of HD procedure was shown when dialyzer was used for 1st and 3rd time. BTG activity increased after 240 min of HI procedure when the dialyzer was used for 3rd time. There was a fall in platelet count after 30 min of HD during the 1st and the 3rd dialyzer use. The fall in platelet count lasted all dialysis session when dialyser was used for 3rd time. The PF4 activity was decreased after 30 min of HD session after the 1st and the 2nd dialyzer use.