Benchmarking of X-Ray Fluorescence Microscopy with Ion Beam Implanted Samples Showing Detection Sensitivity of Hundreds of Atoms.

Single impurities in insulators are now often used for quantum sensors and single photon sources, while nanoscale semiconductor doping features are being constructed for electrical contacts in quantum technology devices, implying that new methods for sensitive, non-destructive imaging of single- or few-atom structures are needed. X-ray fluorescence (XRF) can provide nanoscale imaging with chemical specificity, and features comprising as few as 100 000 atoms have been detected without any need for specialized or destructive sample preparation. Presently, the ultimate limits of sensitivity of XRF are unknown - here, gallium dopants in silicon are investigated using a high brilliance, synchrotron source collimated to a small spot. It is demonstrated that with a single-pixel integration time of 1 s, the sensitivity is sufficient to identify a single isolated feature of only 3000 Ga impurities (a mass of just 350 zg). With increased integration (25 s), 650 impurities can be detected. The results are quantified using a calibration sample consisting of precisely controlled numbers of implanted atoms in nanometer-sized structures. The results show that such features can now be mapped quantitatively when calibration samples are used, and suggest that, in the near future, planned upgrades to XRF facilities might achieve single-atom sensitivity.

Dabigatran Etexilate Related Unilateral Adrenal Hemorrhage.

A 63-year-old male presented to our clinic with computed tomography data of a large tumor of the left adrenal gland. The formation is highly suspicious for malignancy with central necrosis and hemorrhage, and a total size of 197/183/201 mm. Due to elevated D-dimer values of 7.17 mg/l (reference range <0.5 mg/l), treatment with dabigatran etexilate 2x150 mg was prescribed following a cardiology consult. On the third day of therapy, the patient noticed a large swelling in the left abdominal flank, which caused discomfort. No additional symptoms were reported. No previous abdominal surgical interventions or trauma were reported. Following a thorough physical examination, the patient was referred for a computer tomography that reported a diagnosis of a tumor of the left adrenal gland. Due to the size of the neoplasm, the suspicion of malignancy, compression of adjacent structures, and significant anemia with an Hb of 112 g/L, operative treatment was chosen as the best treatment modality. The mass was reported as a large organizing adrenal hematoma with no suspicion of malignancy on histology. Following a review of available literature, no other cases of unilateral adrenal hematoma with a size of 201x197 mm, following oral anticoagulant therapy with dabigatran etexilate, without any prior surgery or trauma have been reported. Most clinical cases report bilateral adrenal hemorrhage during the postoperative period, following prophylaxis with heparin and the development of heparin-induced thrombocytopenia. The patient underwent operative treatment, after which the patient recovered normally and was discharged from the clinic without complications.

KRAS Mutation Status in Bulgarian Patients with Advanced and Metastatic Colorectal Cancer.

RAS somatic variants are predictors of resistance to anti-EGFR therapy for colorectal cancer (CRC) and affect the outcome of the disease. Our study aimed to evaluate the frequency of RAS, with a focus on KRAS variants, and their association with tumor location and some clinicopathological characteristics in Bulgarian CRC patients. We prospectively investigated 236 patients with advanced and metastatic CRC. Genomic DNA was extracted from FFPE tumor tissue samples, and commercially available kits were used to detect RAS gene somatic mutations via real-time PCR. A total of 115 (48.73%) patients tested positive for RAS mutations, with 106 (44.92%) testing positive for KRAS mutations. The most common mutation in exon 2 was c.35G>T p.Gly12Val (32.56%). We did not find a significant difference in KRAS mutation frequency according to tumor location. However, patients with a mutation in exon 4 of KRAS were 3.23 times more likely to have a tumor in the rectum than in other locations (95% CI: 1.19-8.72, p = 0.021). Studying the link between tumor location and KRAS mutations in exon 4 is crucial for better characterizing CRC patients. Further research with larger cohorts, especially in rectal cancer patients, could provide valuable insights for patient follow-up and treatment selection.

Frantz Tumor: A Case Report of Solid Pseudopapillary Tumor of Pancreas.

The solid pseudopapillary tumor (SPT) is a rare pancreatic lesion that usually affects young and middle-aged patients and has a female predominance and low malignant potential. The exact histogenesis of this tumor is still unclear. We present the case of a 60-year-old female patient with occasional abdominal pain. Positron emission tomography/computed tomography (PET/CT) and magnetic resonance imaging (MRI) revealed a tumor mass in the pancreatic tail. Distal pancreatectomy and splenectomy were performed. The result from the pathology report was solid pseudopapillary neoplasm (SPN). The patient underwent four cycles of adjuvant chemotherapy with gemcitabine, which she tolerated well without complaints. A control computed tomography (CT) scan and PET/CT of the abdomen (five months after the operation) showed a cystic lesion suspicious for local recurrence in the pancreatic tail during the follow-up period. The patient underwent a second surgery operation. Subsequent histological examination showed chronic indurative pancreatitis, areas with steatonecrosis, lipogranulomas, and fibrosis without evidence of relapse. SPT is a rare pancreatic tumor that most commonly affects young women. Although the tumor has locally aggressive characteristics, the prognosis is excellent after surgical excision. Our case emphasizes that this tumor can occur not only in young women but also in older patients. Chronic granulomatous inflammation and indurative pancreatitis can sometimes mimic a relapse on CT and PET/CT image tests.

Feasibility and Safety of Robotic-Assisted Surgery for Rectal Cancer: Short-Term Outcomes of a Pilot Study with da Vinci Xi Platform During COVID-19.

Background: Colorectal cancer is a major cause of morbidity and mortality in the world. Approximately, one of three diagnosed colorectal cancers is a rectal cancer. Recent developments in the field of rectal surgery have promoted the use of surgical robots, which are of great need when surgeons face anatomical difficulties, such as a narrowed male pelvis, bulky tumor, or obese patients. This study aims to evaluate the clinical results of robotic rectal cancer surgery during the introduction period of a surgical robot system. Moreover, the period of the introduction of this technique coincided with the first year of the COVID-19 pandemic. Methods: Since December 2019, the Surgery Department of the University Hospital of Varna has become the newest and the most modern Robotic Surgery Center of Competence in Bulgaria, equipped with the most advanced da Vinci Xi surgical system. From January 2020 to October 2020 a total number of 43 patients have underwent surgical treatment, of which 21 had roboticassisted procedures and the rest - open procedures. Results: Patient characteristics were close between the studied groups. The mean patient age in robotic surgery was 65 years, as six of these patients were females, while in case of open surgery these values were to 70 and 6, respectively. Two thirds (66.7%) of the patients operated on with da Vinci Xi were with tumor stage 3 or 4 and approximately 10% had the tumor located in the lower part of the rectum. The median value of the operation time was 210 min, while the length of hospital stay was 7 days. These short-term parameters were not found to have a large difference in respect to the open surgery group. A significant difference is depicted for the number of lymph nodes resected and the blood loss, with both parameters demonstrating advantage for the robot-assisted surgery. The blood loss is more than twice less than the case of open surgery. Conclusions: The results confidently showed the successful introduction of the robot-assisted platform in the surgery department despite the limitations caused by the COVID-19 pandemic. This technique is expected to become the main choice of minimally invasive technique applied to all types of colorectal cancer surgery in the Robotic Surgery Center of Competence.

A filament 3D printing approach for CT-compatible bone tissues replication.

PURPOSE: The aim of this study is the development of a methodology for manufacturing 3D printed anthropomorphic structures, which mimic the X-ray properties of the human bone tissue. METHODS: A mixing approach of two different materials is proposed for the fabrication of a radiologically equivalent hip bone for an anthropomorphic abdominal phantom. The materials employed for the phantom were polylactic acid (PLA) and Stonefil, while a custom-made dual motor filament extrusion setup and a custom-made software associating medical images directly with the 3D printing process were employed. RESULTS: Three phantoms representing the hip bone were 3D printed utilizing two filaments under three different printing scenarios. The phantoms are based on a patient's abdominal CT scan images. Histograms of CT scans of the printed hip bone phantoms were calculated and compared to the original patient's hip bone histogram, demonstrating that a constant mixing composition of 30% Stonefil and 70% PLA with 0.0375 extrusion rate per voxel (93.75% flow for fulfilling a single voxel) for the cancellous bone, and using 100% Stonefil with 0.04 extrusion rate per voxel (100% flow) for the cortical bone results in a realistic anatomy replication of the hip bone. Reproduced HU varied between 700 and 800, which are close to those of the hip bone. CONCLUSIONS: The study demonstrated that it is possible to mix two different filaments in real-time during the printing process to obtain phantoms with realistic and radiographically bone tissue equivalent attenuation. The results will be explored for manufacturing a CT-compatible abdominal phantom.

Computer aided preoperative evaluation of the residual liver volume using computed tomography images.

Major hepatectomy causes a risk of postoperative liver dysfunction, failure, and infections like surgical site infection. Preoperative assessment of the liver volume and function of the remnant liver is a mandatory prerequisite before performing such surgery. The aim of this work is to develop and test a software application for evaluation of the residual function of the liver prior to the intervention of the surgeons. For this purpose, a technique for evaluation of liver volume from computed tomography (CT) images has been developed. Furthermore, the methodology algorithms were implemented and incorporated within a software tool with three basic functionalities: volume determination based on segmentation of liver from CT images, virtual tumour resection and estimation of the residual liver function and 3D visualisation. Forty-one sets of abdominal CT images consisting of different number of tomographic slice images were used to test and evaluate the proposed approach. Volumes that were obtained after manual tracing by two surgeon experts showed a relative difference of 3.5 %. The suggested methodology was encapsulated within an application with user-friendly interface that allows surgeons interactively to perform virtual tumour resection, to evaluate the relative residual liver and render the final result. Thereby, it is a tool in the surgeons' hands that significantly facilitates their duties, saves time, and allows them to objectively evaluate the situation and take the right decisions. At the same time, the tool appears to be appropriate educational instrument for virtual training of young surgeon specialists.

Virilizing adrenal oncocytoma in a 9-year-old girl: rare neoplasm with an intriguing postoperative course.

Adrenal oncocytoma is an extremely rare neoplasm, which is mostly non-functional. Only five cases of childhood adrenal oncocytoma have been described so far, all of which were hormonally active. Currently, guidelines for management and follow-up are not available. We report a 9-year-old girl with benign adrenal oncocytoma, presenting with severe short-term virilization. After diagnostic work-up the patient underwent laparoscopic unilateral adrenalectomy. For the first 2 weeks following surgery she suffered marked mood swings, irritability and fatigue. There were no other clinical and/or laboratory abnormalities except the rapid drop-down of androgen levels to normal values. Follow-up showed no signs of recurrence and in the absence of signs of adrenal insufficiency, we speculate that, the rapid drop of androgen levels after removal of the tumor might be the reason for the deteriorated psychoemotional condition of our patient.

The role of 3-D endorectal ultrasound in rectal cancer: our experience.

In the last 20 years, endorectal ultrasound (ERUS) has been one of the main diagnostic methods for locoregional staging of rectal cancer. ERUS is accurate modality for evaluating local invasion of rectal carcinoma into the rectal wall layers (T category). Adding the three-dimensional modality (3-D) increases the capabilities of this diagnostic tool in rectal cancer patients. We review the literature and report our experience in preoperative 3-D ERUS in rectal cancer staging. In the group of 71 patients, the staging of preoperative 3-D endorectal ultrasonography was compared with the postoperative morphologic examination. Three-dimensional ERUS preoperative staging was confirmed with morphologic evaluation in 66 out of 71 cases (92.9%). The detection sensitivities of rectal cancer with 3-D ERUS were as follows: T1, 92.8%; T2, 93.1%; T3, 91.6%; and T4, 100.0%; with specificity values of T1, 98.2%; T2, 95.4%; T3, 97.8%; and T4, 98.5%. Three-dimensional ERUS correctly categorized patients with T1, 97.1%; T2, 94.3%; T3, 95.7%; and T4, 98.5%. The percentage of total overstaged cases was 2.75% and that of understaged cases was 6.87%. The metastatic status of the lymph nodes was determined with a sensitivity of 79.1% (19 of 24), specificity of 91.4% (43 of 47), and diagnostic accuracy of 87.3% (62 of 71). In our experience, 3-D ERUS has the potential to become the diagnostic modality of choice for the preoperative staging of rectal cancer.

Impact of each individual component of the mutated PTS(Nag) on glucose uptake and phosphorylation in Ralstonia eutropha G⁺1.

A recent study of the UV-generated glucose-utilizing mutant Ralstonia eutropha G⁺1 comprising transcriptomic and proteomic analyses revealed clear evidence that glucose is transported by the N-acetylglucosamine-specific phosphotransferase system (PTS(Nag)), which is overexpressed in this mutant due to a derepression of the encoding nag operon by an identified insertion mutation in nagR (Raberg et al., Appl Environ Microbiol 77:2058-2070, 2011). The inability of the defined deletion mutant R. eutropha G⁺1∆nagFEC to utilize glucose confirms this finding. Furthermore, a missense mutation in nagE (membrane component comprising the cell membrane spanning EIIC(Nag) and the cytosolic domain EIIB(Nag)) was identified, which yields a substitution of an alanine by threonine at aa 153 of NagE and may affect glucose specificity of the mutated PTS(Nag) in R. eutropha G⁺1. The investigation of various generated deletion and substitution mutants of R. eutropha H16 and G⁺1 in this study was able to elucidate these phenomena. It could be shown that the porin NagC, encoded by nagC being part of the nag operon, is not necessary, while NagE is required and is probably responsible for glucose transport through the cell membrane. The intracellular phosphorylation of glucose is obviously mediated by the glucokinase GLK and not by NagF (cytosolic component comprising the three soluble domains EIIA(Nag), HPr(Nag), and EI(Nag)). Our data clearly indicate that the derepression of the nag operon is essential for glucose uptake. The point mutation in NagE is not an essential prerequisite for glucose transport although it increased glucose transport as observed in this study.