RENAL-CELL CARCINOMA METASTASES TO THE SKIN - A NOT SO RARE CASE

Objective To describe the clinical, histological, immunohistochemical and behavioural patterns of the metastases of renal cell carcinoma to the skin. Patients and methods In a retrospective review of 132 cases of renal cell carcinoma submitted for examination to the Anticancer Institute ‘St Savas’ nine patients with metastatic disease to the skin were discovered. Clinical data and follow-up information were collected and correlated to tumour behaviour and patient survival, Immunohistochemical studies with epithelial membrane antigen (EMA), vimentin, keratin and carcino-embryonic antigen (CEA) were performed. Results In six of the nine patients the skin metastasis was the first evidence of a tumour, Histology of the skin nodule led to identification of the primary site, Histological proof of the renal origin of the tumour was obtained using the above immunohistochemical studies. All patients died from their disease within 3 years of presenting with the skin metastases. Conclusion Metastases to the skin from a renal cell carcinoma as first evidence of the disease may not be as rare as the literature describes. Definite proof of the origin of the tumour requires specialized immunohistochemical techniques

The effect of insect meal as a feed ingredient on survival, growth, and metabolic and antioxidant response of juvenile prawn Palaemon adspersus (Rathke, 1837)

For successful prawn aquaculture, feeds should be based on readily consumed ingredients that promote survival and optimal growth performance. This pilot study investigates the rearing of juvenile Baltic prawn Palaemon adspersus. Two feeding trials were carried out for 60 days; both incorporated insect meals, the first one in fishmeal-based diets, whereas the second one in plant meal ones. Insect meals derived from larvae of Tenebrio molitor (TM), Hermetia illucens (HI) and Musca domestica (MD) were tested as feed ingredients. This study indicated that the inclusion of HI in fishmeal diets resulted in significantly higher growth performance and survival of the prawns, whereas the MD diet led to similarly high growth performance reducing significantly their survival. Growth performance was not affected by the insect inclusion in the plant-based diets, but survival was higher in the TM and HI inclusion diets. The inclusion of TM and HI resulted in higher protein and energy content of the prawns’ muscle when incorporated in fishmeal and plant meal diets respectively. No significant differences were observed in the activities of hepatopancreas’ amino acid-catabolizing enzymes. Concluding, the combinations fishmeal–HI and plant meal–TM can be used for the successful rearing of Baltic prawn. © 2020 John Wiley & Sons Lt

Evaluation of the Icare-ONE rebound tonometer as a self-measuring intraocular pressure device in normal subjects

Purpose To compare Icare ONE rebound self-tonometer (ICRBT)measurements withGoldman applanation tonometry (GAT). Methods A trained examiner instructed each of 60 normal subjects on use of the ICRBT. Each subject then took two measurements of his/her own pressure using the ICRBT. Finally, a different examiner, who was masked to the earlier readings, measured IOP by GAT. Bland-Altman limits of agreement (LOA), intraclass correlation coefficients (ICCs), Kappa values, and paired t-test were used to assess the agreement between the two methods. Pearson's correlation coefficient was used for correlation analysis. Results All of the subjects were able to obtain correct measurements with ICRBT after three attempts. The mean intraocular pressure with ICRBT and GAT measurements were 16.0±3.3 mmHg and 13.7±2.5 mmHg respectively. The mean difference between patient's ICRBT and technician's GAT measurements was 2.3 mmHg (p<0.001). In 63 % (38/60) of the cases the IOP difference (ICRBT - GAT) was within±3 mmHg. The weighted Kappa for the IOP measurements of the two methods was 0.49 (95% CI: 0.30-0.68, p< 0.001), indicating acceptable agreement. A significantly positive correlation was found between ICRBT IOP measurements and central corneal thickness (CCT) (r=0.48, p< 0.001). In addition, the difference in IOP measurements (ICRBT - GAT) between the two methods was positively correlated with CCT (r=0.31, p=0.015), indicating that greater thickness is associated with greater differences between the two methods. Conclusion The ICRBT was reliable in the hands of normal subjects, and may be used for self-monitoring of IOP. ICRBT measurements generally overestimated GAT measurements. © Springer-Verlag 2012

Study of patients with ocular hypertension with scanning laser polarimetry and short-wavelength automatic perimetry

Aims: To compare and correlate retinal nerve fiber layer (RNFL) measurements obtained by scanning laser polarimetry (SLP) with defects detected by short-wavelength automatic perimetry (SWAP) in eyes with ocular hypertension (OHT). Methods: SLP and SWAP were performed in 96 eyes of 48 consecutive patients with OHT. Results: Twenty-five eyes (26%) had SWAP visual field defects. Twenty-seven eyes (28.1%) had abnormal RNFL evaluation defined by the GDx neural network ('number'>29). Fourteen eyes of 10 patients (14.5%) had abnormal RNFL evaluation and SWAP visual field defects. RNFL thickness measurements were significantly reduced in eyes with abnormal SWAP. A weak but statistically significant correlation between the 'number' and pattern standard deviation (r = 0.3, p = 0.006) and the corrected pattern standard deviation (r = 0.3, p = 0.007) in SWAP was found. Areas of abnormal RNFL thickness corresponded to the localization of the SWAP visual field defects in corrected pattern deviation plots in 10 of the 14 eyes with defects in both tests. Conclusions: SWAP visual field defects frequently coexist and correspond with abnormalities of RNFL detected by SLP in eyes with OHT. In certain eyes, however, the two methods detect different glaucoma properties. Copyright © 2006 S. Karger AG

Clinical activity of an htert-specific cancer vaccine (Vx-001) in “immune desert” NSCLC

Background: Tumors can be separated into immunogenic/hot and non-immunogenic/cold on the basis of the presence of tumor-infiltrating lymphocytes (TILs), the expression of PD-L1 and the tumor mutation burden (TMB). In immunogenic tumors, TILs become unable to control tumor growth because their activity is suppressed by different inhibitory pathways, including PD-1/PD-L1. We hypothesized that tumor vaccines may not be active in the immunosuppressive microenvironment of immunogenic/hot tumors while they could be efficient in the immune naïve microenvironment of non-immunogenic/cold tumors. Methods: The randomized phase II Vx-001-201 study investigated the effect of the Vx-001 vaccine as maintenance treatment in metastatic non-small cell lung cancer (NSCLC) patients. Biopsies from 131 (68 placebo and 63 Vx-001) patients were retrospectively analyzed for PD-L1 expression and TIL infiltration. TILs were measured as tumor-associated immune cells (TAICs), CD3-TILs, CD8-TILs and granzyme B-producing TILs (GZMB-TILs). Patients were distinguished into PD-L1(+) and PD-L1(-) and into TIL high and TIL low. Findings: There was no correlation between PD-L1 expression and Vx-001 clinical activity. In contrast, Vx-001 showed a significant improvement of overall survival (OS) vs. placebo in TAIC low (21 vs. 8.1 months, p = 0.003, HR = 0.404, 95% CI 0.219–0.745), CD3-TIL low (21.6 vs. 6.6 months, p < 0.001, HR = 0.279, 95% CI 0.131–0.595), CD8-TIL low (21 vs. 6.6 months, p < 0.001; HR = 0.240, 95% CI 0.11–0.522) and GZMB-TIL low (20.7 vs. 11.1 months, p = 0.011, HR = 0.490, 95% CI 0.278–0.863). Vx-001 did not offer any clinical benefit in patients with TAIC high, CD3-TIL high, CD8-TIL high or GZMB-TIL high tumors. CD3-TIL, CD8-TIL and GZMB-TIL were independent predictive factors of Vx-001 efficacy. Conclusions: These results support the hypothesis that Vx-001 may be efficient in patients with non-immunogenic/cold but not with immunogenic/hot tumors. © 2021 by the authors. Licensee MDPI, Basel, Switzerland

Comparison of dynamic contour tonometry with Goldmann applanation tonometry in glaucoma practice

Purpose: To compare intraocular pressure (IOP) readings taken using dynamic contour tonometry (DCT) with IOP readings taken with Goldmann applanation tonometry (GAT) in eyes with glaucoma or ocular hypertension. Methods: The present study included 100 eyes in 100 patients with glaucoma or ocular hypertension. After pachymetry DCT and GAT were performed. Intraocular pressures as measured with DCT and GAT were compared with one another and with central corneal thickness (CCT). Results: Mean DCT IOP measurements (20.1 ± 4.3 mmHg) were significantly (p < 0.001) higher than GAT IOP values (17.9 ± 4.7 mmHg). The mean difference between DCT and GAT measurements was 2.1 mmHg (range - 3.4 to 9.7 mmHg). The difference followed a normal distribution. Measurements made with DCT and GAT correlated significantly with one another (Spearman's rho = 0.761, p < 0.001). Neither GAT nor DCT measurements showed a significant correlation with CCT (537 ± 39 μm, range 458-656 μm). Multivariate regression analysis has shown that the difference between DCT and GAT is influenced significantly by ocular pulse amplitude (r = - 0.334, p = 0.001) and it is not influenced by CCT (r = - 0.106, p = 0.292). Conclusions: In eyes with glaucoma or ocular hypertension, DCT facilitates suitable and reliable IOP measurements which are in good concordance with GAT readings. Variation in CCT cannot by itself explain the differences in measurements taken with DCT and GAT in a number of eyes. © 2008 Acta Ophthalmol

Generation of non‐small cell lung cancer patient‐derived xenografts to study intratumor heterogeneity

Recent advances in sequencing technologies have allowed the in‐depth molecular study of tumors, even at the single cell level. Sequencing efforts have uncovered a previously unappreci-ated heterogeneity among tumor cells, which has been postulated to be the driving force of tumor evolution and to facilitate recurrence, metastasis, and drug resistance. In the current study, focused on early‐stage operable non‐small cell lung cancer, we used tumor growth in patient‐derived xeno-graft (PDX) models in mice as a fast‐forward tumor evolution process to investigate the molecular characteristics of tumor cells that grow in mice, as well as the parameters that affect the grafting efficiency. We found that squamous cell carcinomas grafted significantly more efficiently compared with adenocarcinomas. Advanced stage, patient age and primary tumor size were positively correlated with grafting. Additionally, we isolated and characterized circulating tumor cells (CTC) from patients’ peripheral blood and found that the presence of CTCs expressing epithelial‐to‐mesenchy-mal (EMT) markers correlated with the grafting potential. Interestingly, exome sequencing of the PDX tumor identified genetic alterations in DNA repair and genome integrity genes that were un-der‐represented in the human primary counterpart. In conclusion, through the generation of a PDX biobank of NSCLC, we identified the clinical and molecular properties of tumors that affected growth in mice. © 2021 by the authors. Licensee MDPI, Basel, Switzerland

Endoscopic transgastric procedures in anesthetized pigs: technical challenges, complications, and survival

Background and study alms: An incisionless endoscopic peroral transgastric approach to the peritoneal cavity has shown promise in animals as a potentially less invasive form of surgery. We present our experience with various endoscopic peroral transgastric procedures, reporting on the technical aspects and challenges that arose. Materials and methods: The following procedures were performed in 10 anesthetized pigs using a double-channel endoscope: peritoneoscopy (10 pigs), liver biopsy (one pig), cholecystectomy (six pigs), fallopian tube excision (one pig), and hysterectomy (one pig). Results: All the procedures were accomplished successfully. There were six minor intraoperative complications. Complete gastric cleansing and elimination of all bacteria was found to be impossible to achieve in the porcine model. Overinflation was a common problem. The lack of adequate endoscope support was a major limitation. Safe closure of the gastrotomy incision was difficult using the available clipping devices. Six pigs made an uncomplicated recovery after a follow-up period of 4-6 weeks. Subsequent pathological examination revealed deep gastric ulceration in one animal and a gastric wall abscess in another. Conclusions: Peroral transgastric surgery is technically feasible and safe in a porcine model. Although all the procedures were performed successfully, the study highlights some technical difficulties and illustrates the need for major technical innovations and extensive animal studies in order to evaluate the merits of incisionless surgery

The Role of CXCL13 and CXCL9 in Early Breast Cancer

Background: Chemokines, cytokines in the immune microenvironment of tumors, may be associated with patient outcome. We assessed the impact of CXCL13 and CXCL9 on disease-free (DFS) and overall survival (OS), in an attempt to retrospectively evaluate both T and B cell function in the microenvironment of primary tumors from patients with breast cancer. Materials and Methods: Formalin-fixed paraffin-embedded tissue blocks from patients with intermediate/high-risk, early breast cancer, treated with sequential adjuvant epirubicin, paclitaxel, and cyclophosphamide methotrexate fluorouracil within a randomized trial, were tested for CXCL13 and CXCL9 messenger RNA expression; 557 patients with adequate tissue were eligible for the analysis. Results: CXCL13 was correlated with CXCL9 (rho = 0.52; P < .001). High-expressing CXL13 and CXCL9 tumors had higher Ki67 and tumor infiltrating lymphocyte density (P-values < .001). High CXCL9 expression was an unfavorable prognosticator for OS among all patients (hazard ratio [HR], 1.73; P = .021), whereas it showed favorable significance for both DFS and OS in patients with triple negative disease (HR, 0.29; P = .027 and HR, 0.32; P = .045). High CXCL13 conferred longer DFS and OS among patients with luminal-human epidermal growth factor receptor 2 disease (HR, 0.31; P = .013 and HR, 0.25; P = .005). Patients with low CXCL13 and high CXCL9 expression had shorter DFS and OS compared with those with high expression of both chemokines (HR, 1.63; P = .006 and HR, 1.61; P = .016). Conclusions: Both biomarkers were associated with poor prognosis characteristics and with tumor infiltrating lymphocyte density. High CXCL9 conferred an improved prognosis in the triple negative subtype, whereas high CXCL13 was associated with improved outcome in the luminal-human epidermal growth factor receptor 2 subtype. Chemokines can be associated with breast cancer subtype and outcome. These data should be evaluated prospectively. © 2019 Elsevier Inc. Chemokines are of increasing interest in breast cancer. A total of 557 tissue samples from patients with early breast cancer treated in the context of a prospective adjuvant chemotherapy trial were tested for CXCL13 and CXCL9 expression, and the results were associated with outcome and other markers. CXCL13 was associated with triple positive disease and CXCL9 with triple negative disease, both conferring improved outcome. © 2019 Elsevier Inc