Unlike metastatic colorectal cancer (CRC) there are to date few reports concerning the predictive value of molecular biomarkers on the clinical outcome in stage II/III CRC patients receiving adjuvant ...chemotherapy. Aim of this study was to assess the predictive value of proteins related with the EGFR- and VEGFR- signalling cascades in these patients.
The patients' data examined in this study were from the collective of the 5-FU/FA versus 5-FU/FA/irinotecan phase III FOGT-4 trial. Tumor tissues were stained by immunohistochemistry for VEGF-C, VEGF-D, VEGFR-3, Hif-1 α, PTEN, AREG and EREG expression and evaluated by two independent, blinded investigators.
Patients with negative AREG and EREG expression on their tumor had a significant longer DFS in comparison to AREG/EREG positive ones (p< 0.05). The benefit on DFS in AREG-/EREG- patients was even stronger in the group that received 5-FU/FA/irinotecan as adjuvant treatment (p=0.002). Patients with strong expression of PTEN profited more in terms of OS under adjuvant treatment containing irinotecan (p< 0.05). Regarding markers of the VEGFR- pathway we found no correlation of VEGF-C- and VEGFR-3 expression with clinical outcome. Patients with negative VEGF-D expression had a trend to live longer when treated with 5-FU/FA (p=0.106). Patients who were negative for Hif-1 α, were disease-free in more than 50% at the end of the study and showed significant longer DFS-rates than those positive for Hif-1 α (p=0.007). This benefit was even stronger at the group treated with 5-FU/FA/irinotecan (p=0.026). Finally, AREG-/EREG-/PTEN+ patients showed a trend to live longer under combined treatment combination.
The addition of irinotecan to adjuvant treatment with 5-FU/FA does not provide OS or DFS benefit in patients with stage II/III CRC. Nevertheless, AREG/EREG negative, PTEN positive and Hif-1 α negative patients might profit significantly in terms of DFS from a treatment containing fluoropyrimidines and irinotecan. Our results suggest a predictive value of these biomarkers concerning adjuvant chemotherapy with 5-FU/FA +/- irinotecan in stage II/III colorectal cancer.
AbstractThe use of multisensor system (MSS) plays a key role in engineering geodesy. Because of the complexity of tasks such as industrial applications with high accuracy requirements for ...heterogeneous and efficient three-dimensional (3D) data acquisition, kinematic MSS are often used. Traditionally, these MSS are composed of referencing sensors and object-capturing sensors. The crucial point in a MSS setup is the determination of the mutual position and orientation six degrees of freedom (6 DOF) of each sensor. Within this contribution, a possibility for the determination of the 6 DOF of light detection and ranging (LiDAR) sensors in MSS is introduced. The presented approach is generally applicable and allows the 6 DOF determination of profile laser scanners. The 6 DOF and their uncertainty measures are estimated within an adjustment model by utilizing known reference geometries (RFGs). The approach is especially of interest when sensor origins are not physically available and measurable. It is generally applicable in a static or kinematic measurement environment. As an example, the approach is applied in an industrial environment with accuracy requirements of a few millimeters. The used MSS consists of a terrestrial laser scanner (object capturing) and a laser tracker (referencing). The linking component is a tracker-machine control sensor, which is attached to the laser scanner. More precisely, 6 DOF between the tracker-machine control sensor and the origin of the laser scanner have to be determined. Depending on the required accuracy of the 3D object acquisition, the determination of the 6 DOF must fulfill high accuracy requirements. Finally, the results and the accuracy of the 6 DOF determination are shown and validated with a static calibration procedure.
The solid-state molecular structure of centrohexaindane (), a unique hydrocarbon comprising six benzene rings clamped to each other in three dimensions around a neopentane core, and the molecular ...packing in crystals of ·CHCl3 are reported. The molecular Td-symmetry and the Cartesian orientation of the six indane wings of in the solid state have been confirmed. The course and limitation of electrophilic aromatic substitution of are demonstrated for the case of nitration. Based on nitration experiments of a lower congener of , tribenzotriquinacene , the six-fold nitrofunctionalisation of has been achieved in excellent yield, giving four constitutional isomers, two nonsymmetrical ( and ) and two C3-symmetrical ones ( and ), all of which contain one single nitro group in each of the six benzene rings. The relative yields of the four isomers (∼3 : 1 : 1 : 3) point to a random electrophilic attack of the electrophiles at the twelve formally equivalent outer positions of the aromatic periphery of , suggesting electronic independence of its six aromatic π-electron systems. In turn, the pronounced conformational rigidity of the centrohexacyclic framework of enables the unequivocal structural identification of the isomeric hexanitrocentrohexaindanes by (1)H NMR spectroscopy.
The prostate cancer antigen 3 (PCA3) gene urine assay is established for biopsy decision in case of prostate cancer (PC) suspicion. Recent findings pointed to an age dependence of PCA3, with putative ...impact on test interpretation. However, to date no experience has been reported with regard to the extent age might modify the score in certain age ranges. Therefore, the aim of the present study was to re-evaluate the age dependency and, moreover, give suggestions for interpretation of the PCA3 score in dependence of patient's age in daily routine.
The study comprised 684 patients before prostate biopsy or prostatectomy. Post-massage voided urine samples were assessed by PCA3 measurement. PCA3 scores were correlated to patient's age. The collective was divided into four subcollectives by quartiles of age distribution. For every subcollective the cutoff value at specificity of ≥ 60 was determined. Results were classified by age-class specific cutoff values and test qualities were compared at different cutoffs.
In the collective, 59.1% of patients had a positive biopsy. PCA3 correlated to patient's age in univariate and multivariate analysis (p < 0.001 each). The division into age subcollectives revealed groups < 60, 60 - 65, 66 - 69 and > 69 years. Median PCA3 values of patients without/with PC were 17/32, 27/42, 34/55 and 52/68 in the four age classes. Cutoff values for which specificity was determined with ≥ 60 were 23, 39, 42, and 65. Constant cutoff values showed lower sensitivities in younger and lower specificities in older patients. Only the age adjusted values revealed an improved performance with PPV 68.7, accuracy 59.5 and sensitivity 57.7 at specificity of 62.1% in the whole cohort.
The study confirms that the PCA3 score increases with age. The recommended cutoff score of 35 is suitable especially for patients aged in their sixties. Lower reference values between 20 and 30 have to be taken into account in patients aged < 60 years and higher values around 40 to 50 may point to suspicion for PC in patients > 69 years. These results may further improve the diagnostic performance of the PCA3 test and keep the PCA3 test as a significant test in PC diagnostics along with new upcoming urine markers.
Paroxysmal atrial fibrillation (PAF) is often asymptomatic but nonetheless harmful. We evaluated the performance of disease-related blood biomarkers and CHA2DS2-VASc score to discriminate for PAF in ...patients with continuous rhythm monitoring.
Clinical data and blood samples were obtained from patients with dual-chamber pacemakers selected according to the absence (no_AHRE) or presence of Atrial High-Rate Episodes (AHRE) >6 min in recent device history (case-control approach). We included 93 patients (n = 49 AHRE, n = 44 no_AHRE). In a subgroup with high AHRE burden and confirmed PAF 15 biomarkers were evaluated (n = 19 AHRE-AF vs. n = 20 no_AHRE). Significantly regulated biomarkers were then tested in all patients to distinguish no_AHRE from AHRE (receiver operating characteristics analysis). Hsp27, TGFβ1, cystatin C, matrix metalloproteinases MMP-2,-3,-9, albumin, and serum uric acid were not altered in the subgroup. Tissue inhibitors of metalloproteinases (TIMP) -1,-2,-4; NT-proANP, NT-proBNP, IL-6 and serum amyloid protein A were significantly different in AHRE vs. no_AHRE (subgroup and whole cohort), with best discriminatory performance for TIMP-4. Biomarkers performed better than CHADS2-VASc for AHRE discrimination. Intracardial electrograms and medical history from seven AHRE patients suggested atrial tachycardia and not AF (AHRE-AT). Four of the most relevant regulated biomarkers (TIMP-4, TIMP-2, SAA, NT-proBNP) behaved similarly in AHRE-AT and AHRE-AF. NT-proBNP >150 pg/mL indicated an odds ratio of 12.9 for AHRE. Combining two biomarkers significantly improved discrimination of AHRE.
TIMP-4, NT-proANP, NT-proBNP were strongest associated with PAF and AHRE. The discriminatory performance of CHADS2-VASc for PAF was increased by addition of selected biomarkers.
The Cover Feature shows carboranyl analogues of celecoxib, a potent COX‐2‐selective inhibitor (COXIB). Cyclooxygenase‐2 (COX‐2) has a prominent role in the occurrence and progression of various ...cancers. Recently, there is an expressed focus on the development of new COX‐2‐selective inhibitors (COXIBs) as potential cytostatic agents. A highly stable carborane cluster, which can serve as phenyl mimetic, was implemented in the structure of celecoxib in order to generate analogues with enhanced metabolic stability. Although the new derivatives do not act as COXIBs, they proved to have a potent cytostatic effect on various melanoma and colon cancer cell lines. Cover illustration by Menyhárt‐Botond Sárosi. More information can be found in the Full Paper by Evamarie Hey‐Hawkins et al. on page 315 in Issue 3, 2019 (DOI: 10.1002/cmdc.201800685).
In this observational study, patient-reported outcomes and short-term clinical outcome parameters in patients with colorectal cancer were studied 12 months after the start of treatment. Outcomes were ...also compared across German Certified Colorectal Cancer Centres.
Data were collected from 4239 patients with colorectal cancer who had undergone elective tumor resection in one of 102 colorectal cancer centers and had responded to a quality-of-life questionnaire before treatment (EORTC QLQ-C30 and -CR29). 3142 (74.1%) of these patients completed a post-treatment questionnaire 12 months later. Correlation analyses were calculated and case-mix adjusted comparisons across centers were made for selected patient-reported outcomes, anastomotic insufficiency, and 30-day-mortality.
At 12 months, mild improvements were seen in mean quality-of-life scores (66 vs. 62 points), constipation (16 vs. 19), and abdominal pain (15 vs. 17). Worsening was seen in physical function (75 vs. 82) and pain (22 vs. 19). Better patient-reported outcomes at 12 months were associated with better scores before treatment. Better results in at least three of the five scores were associated with male sex, higher educational level, higher age, and private health insurance. Major worsening of fecal incontinence was seen among patients with rectal cancer without a stoma. The largest differences across centers were found with respect to physical function. Anastomotic insufficiency was found in 4.3% of colon cancer patients and 8.2% of rectal cancer patients. 1.9% of patients died within 30 days after their resection.
Clinicians can use these findings to identify patients at higher risk for poorer patient-reported outcomes. The differences among cancer centers that were found imply that measures for quality improvement would be desirable.
The number of virtual reality (VR) simulators is increasing. The aim of this prospective trial was to determine the benefit of VR cystoscopy (UC) and transurethral bladder tumor resection (TURBT) ...training in students.
Medical students without endoscopic experience (n=51, median age=25 yr, median 4th academic year) were prospectively randomized into groups A and B. After an initial VR-UC and VR-TURBT task, group A (n=25) underwent a video-based tutorial by a skilled expert. Group B (n=26) was trained using a VR training program (Uro-Trainer). Following the training, every participant performed a final VR-UC and VR-TURBT task. Performance indicators were recorded via the simulator. Data was analyzed by Mann-Whitney U test.
VR cystoscopy and TURBT.
No baseline and post-training differences were found for VR-UC between groups. During baseline, VR-TURBT group A showed higher inspected bladder surface than group B (56% vs 73%, p=0.03). Subgroup analysis detected differences related to sex before training (male: 31.2% decreased procedure time; 38.1% decreased resectoscope movement; p=0.02). After training, significant differences in procedure time (3.9min vs 2.7min, p=0.007), resectoscope movement (857mm vs 529mm, p=0.005), and accidental bladder injury (n=3.0 vs n=0.88, p=0.003) were found. Male participants showed reduced blood loss (males: 3.92ml vs females: 10.12ml; p=0.03) after training.
Measuring endoscopic skills within a virtual environment can be done easily. Short training improved efficacy and safety of VR-TURBT. Nevertheless, transfer of improved VR performance into real world surgery needs further clarification.
We investigated how students without endoscopic experience profit from simulation-based training. The safe environment and repeated simulations can improve the surgical training. It may be possible to enhance patient’s safety and the training of surgeons in long term.
Simulator training teaches endourological interventions under controlled conditions. Students without endoscopic experience profit from simulation-based training. In conclusion, a simulation-based training is very useful to push the surgical learning curve of future urologist 2.0.
We report the case of a 53-year-old female patient who was transplanted with the liver of a 71-year-old male donor for advanced primary sclerosing cholangitis (PSC) and who additionally was diagnosed ...with a histologically non-classifiable colitis shortly before transplantation. Upon follow-up abdominal ultrasound 4 months after transplantation, a liver lesion measuring 16 × 23 mm was detected in the transplanted liver. This lesion had not been noticed immediately after transplantation and showed a pattern suspicious for malignancy in contrast-enhanced ultrasound. In line, a biopsy revealed the presence of a metastasis of an adenocarcinoma of colorectal origin, suggesting that a colitis- and PSC-associated colorectal cancer of the recipient might have been overseen upon the initial diagnostic workup. Despite two negative follow-up colonoscopies, this hypothesis was further supported by a strong positive signal in projection to the cecum in a subsequently performed PET/CT-scan. However, surgical resection of the right colon that was performed simultaneously with the atypical resection of the liver metastasis only revealed an inflamed diverticulum but no malignancy in the resected colon segment. Moreover, cytogenetic and molecular genetic testing on the resected specimens clearly attributed the metastasis to the male donor. On the one hand, this case underlines the necessity of endoscopic surveillance of patients with PSC and/or inflammatory bowel disease as well as the challenges in diagnosis of colitis-associated cancer. On the other hand, it shows that the acceptance of organs from elderly donors in times of organ shortage might be linked to an increased risk of donor transmitted malignancies.
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