Hereditary Breast Cancer in Romania-Molecular Particularities and Genetic Counseling Challenges in an Eastern European Country.

In Romania, breast cancer (BC) is the most common malignancy in women. However, there is limited data on the prevalence of predisposing germline mutations in the population in the era of precision medicine, where molecular testing has become an indispensable tool in cancer diagnosis, prognosis, and therapeutics. Therefore, we conducted a retrospective study to determine the prevalence, mutational spectrum, and histopathological prediction factors for hereditary breast cancer (HBC) in Romania. A cohort of 411 women diagnosed with BC selected upon NCCN v.1.2020 guidelines underwent an 84-gene NGS-based panel testing for breast cancer risk assessment during 2018-2022 in the Department of Oncogenetics of the Oncological Institute of Cluj-Napoca, Romania. A total of 135 (33%) patients presented pathogenic mutations in 19 genes. The prevalence of genetic variants was determined, and demographic and clinicopathological characteristics were analyzed. We observed differences among BRCA and non-BRCA carriers regarding family history of cancer, age of onset, and histopathological subtypes. Triple-negative (TN) tumors were more often BRCA1 positive, unlike BRCA2 positive tumors, which were more often the Luminal B subtype. The most frequent non-BRCA mutations were found in CHEK2, ATM, and PALB2, and several recurrent variants were identified for each gene. Unlike other European countries, germline testing for HBC is still limited due to the high costs and is not covered by the National Health System (NSH), thus leading to significant discrepancies related to the screening and prophylaxis of cancer.

Prevalence of positive screening test results and agreement between cytology and human papillomavirus testing in primary cervical cancer screening in North-Western Romania.

Using data from a pilot study conducted in North-Western Romania, we aimed to estimate the prevalence of abnormal cytology and positive high-risk human papillomavirus (hr-HPV) test results in an ethnically diverse screening population and to assess the agreement between cytology and hr-HPV testing to evaluate the feasibility of integrating the latter as a primary test in the national cervical cancer screening program. The cross-sectional pilot study included Roma women, other ethnic minorities, and women in rural remote areas. Samples were taken for liquid-based cytology and hr-HPV testing (Hybrid Capture 2 DNA test) by a mobile health unit. The prevalence of positive screening results and the agreement between cytology and hr-HPV testing were estimated by κ coefficient. A total of 1019 women were included in the study. The population prevalence of positive screening results was similar for both tests (12%). The prevalence of abnormal cytology increased with increasing age, whereas the prevalence of positive hr-HPV test showed a bimodal age pattern. Substantial differences in the prevalence of abnormal cytology were found by ethnicity, with highest prevalence in Romanian women (14%), followed by Roma women (6%) and women of other ethnicities (5%) (P = 0.002). Similar ethnic differences in the prevalence of positive hr-HPV test were not observed. The overall agreement of positive screening results between the two methods was fair (κ = 0.25; 95% confidence interval = 0.18-0.30, P < 0.001) and ranged from poor to substantial depending on the age group. The prevalence of abnormal cytology result was high and similar to the prevalence of positive hr-HPV test result, which could allow for the implementation of hr-HPV testing as a primary test in the cervical cancer screening program in Romania.

Increased connective tissue attachment to silicone implants by a water vapor plasma treatment.

Polydimethylsiloxane (PDMS) is the most common type of silicone polymer for the fabrication of implantable medical devices. Because of its inherent hydrophobic nature, the PDMS surface does not readily promote cellular adhesion, which leads to diverse clinical issues. Previously, we reported a simple water vapor plasma treatment of PDMS surfaces that resulted in stable long-term wettability and excellent in vitro cell compatibility. In this work, we report investigation of the in vivo local responses to PDMS implants treated by water vapor plasma using a subcutaneous rat model. The local tissue responses were assessed after 2 and 4 weeks of implantation by means of macroscopic and histomorphometric analysis. After 2 weeks of implantation, the plasma-treated implants elicited the formation of fibrous tissue capsules that were significantly thinner, more adherent, and vascularized than the control counterparts. The improved cell adhesion was correlated with an increased amount of cells attached to the implant surface after retrieval. There was no difference in the inflammatory response between untreated and treated samples. This study provides a rational approach to optimize the long-term performance of silicone implants, which is likely to have a significant impact in clinical applications demanding enhanced tissue integration of the implants.

Cadaveric orthotopic auxiliary split liver transplantation and kidney transplantation: an alternative for type 1 primary hyperoxaluria.

Liver transplantation (LTX) corrects the enzymatic defect responsible for type 1 primary hyperoxaluria (PH1). It has been advocated in combination with kidney transplantation (KTX) in patients with renal failure from PH1 because KTX alone can result in early graft loss. A 58-year-old male patient with PH1 on hemodialysis underwent resection of the left lateral segment of the liver followed by orthotopic auxiliary left lateral segment liver transplantation and kidney transplantation from a deceased donor. The serum oxalate dropped from 34.8 micromol/L before transplant to 3.6-8.3 in the first months posttransplant to <1 micromol/L (normal range 0.4-3.0). One year after posttransplant, the patient has an iothalamate glomerular filtration rate of 58 ml/min. Orthotopic auxiliary LTX is an alternative to whole LTX in PH1. By using a split deceased donor liver, it does not deprive the donor pool and protects the recipient from liver failure in case of graft loss.

A computer assisted method for guide-wore and catheter evaluation.

We developed a method for testing guide wires and catheters that realistically evaluates the forces applied to anatomical structures by these instruments during urological procedures. The placement of guide wires and catheters to gain access to the upper urinary tract can induce undesirable stress on the tissue. Previous studies have characterized wire/catheter performances base on their physical properties, such as stiffness and friction coefficient. However, the results of these studies do not directly quantify their effect on the tissues. Additionally, individual physical properties do not entirely characterize the behavior of the wire/catheter ensemble. Our model utilizes a computer-controlled test stand that simulates the urological environment by including a tortuous path and a stone obstruction. Experimental results indicate that the method shows significant promise in reflecting wire/catheter performance data in congruence with reliable real-life measures of stress upon relevant anatomical structures. Furthermore, due to the modularity of the approach, the model can be easily reconfigured to simulate environments from other medical fields.

Precision placement of instruments for minimally invasive procedures using a "needle driver" robot.

Medical practice continues to move toward less invasive procedures. Many of these procedures require the precision placement of a needle in the anatomy. Over the past several years, our research team has been investigating the use of a robotic needle driver to assist the physician in this task. This paper summarizes our work in this area. The robotic system is briefly described, followed by a description of a clinical trial in spinal nerve blockade. The robot was used under joystick control to place a 22 gauge needle in the spines of 10 patients using fluoroscopic imaging. The results were equivalent to the current manual procedure. We next describe our follow-up clinical application in lung biopsy for lung cancer screening under CT fluoroscopy. The system concept is discussed and the results of a phantom study are presented. A start-up company named ImageGuide has recently been formed to commercialize the robot. Their revised robot design is presented, along with plans to install a ceiling-mounted version of the robot in the CT fluoroscopy suite at Georgetown University.

Robotic assisted radio-frequency ablation of liver tumors--randomized patient study.

The minimally invasive treatment of liver tumors represents an alternative to the open surgery approach. Radio-frequency ablation destroys a tumor by delivering radio-frequency energy through a needle probe. Traditionally, the probe is placed manually using imaging feedback. New approaches use robotic devices to accurately place the instrument at the target. The authors developed an image-guided robotic system for percutaneous interventions using computed tomography. The paper presents a randomized patient study comparing the manual versus robotic needle placement for radio-frequency ablation procedures of liver tumors. The results of this study show that in our case robotic interventions were a very viable solution. Several treatment parameters such as radiation exposures and procedure-times were found to be significantly improved in the robotic case.

Measurement of bio-impedance with a smart needle to confirm percutaneous kidney access.

PURPOSE: The traditional method of percutaneous renal access requires freehand needle placement guided by C-arm fluoroscopy, ultrasonography, or computerized tomography. This approach provides limited objective means for verifying successful access. We developed an impedance based percutaneous Smart Needle system and successfully used it to confirm collecting system access in ex vivo porcine kidneys. MATERIALS AND METHODS: The Smart Needle consists of a modified 18 gauge percutaneous access needle with the inner stylet electrically insulated from the outer sheath. Impedance is measured between the exposed stylet tip and sheath using Model 4275 LCR meter (Hewlett-Packard, Sunnyvale, California). An ex vivo porcine kidney was distended by continuous gravity infusion of 100 cm. water saline from a catheter passed through the parenchyma into the collecting system. The Smart Needle was gradually inserted into the kidney to measure depth precisely using a robotic needle placement system, while impedance was measured continuously. RESULTS: The Smart Needle was inserted 4 times in each of 4 kidneys. When the needle penetrated the distended collecting system in 11 of 16 attempts, a characteristic sharp drop in resistivity was noted from 1.9 to 1.1 ohm m. Entry into the collecting system was confirmed by removing the stylet and observing fluid flow from the sheath. This characteristic impedance change was observed only at successful entry into the collecting system. CONCLUSIONS: A characteristic sharp drop in impedance signifies successful entry into the collecting system. The Smart Needle system may prove useful for percutaneous kidney access.

System for robotically assisted percutaneous procedures with computed tomography guidance.

We present the prototype of an image-guided robotic system for accurate and consistent placement of percutaneous needles in soft-tissue targets under CT guidance inside the gantry of a CT scanner. The couch-mounted system consists of a seven-degrees-of-freedom passive mounting arm, a remote center-of-motion robot, and a motorized needle-insertion device. Single-image-based coregistration of the robot and image space is achieved by stereotactic localization using a miniature version of the BRW head frame built into the radiolucent needle driver. The surgeon plans and controls the intervention in the scanner room on a desktop computer that receives DICOM images from the scanner. The system does not need calibration, employs pure image-based registration, and does not utilize any vendor-specific hardware or software features. In the open air, where there is no needle-tissue interaction, we systematically achieved an accuracy better than 1 mm in hitting targets at 5-8 cm from the fulcrum point. In the phantom, the orientation accuracy was 0.6 degrees, and the distance between the needle tip and the target was 1.04 mm. Experiments indicated that this robotic system is suitable for a variety of percutaneous clinical applications.