Diagnosis and management of indeterminate testicular lesions.

The sophistication and accessibility of modern-day imaging result in frequent detection of small or equivocal lesions of the testes. Traditionally, diagnosis of a testicular lesion with any possibility of malignancy would usually prompt radical orchidectomy. However, awareness is growing that a substantial proportion of these lesions might be benign and that universal application of radical orchidectomy risks frequent overtreatment. Given the potentially profound effects of radical orchidectomy on fertility, endocrine function and psychosexual well-being, particularly in scenarios of an abnormal contralateral testis or bilateral lesions, organ-preserving strategies for equivocal lesions should be considered. Image-based active surveillance can be applied for indeterminate lesions measuring ≤15 mm with a low conversion rate to surgical treatment. However, these outcomes are early and from relatively small, selected cohorts, and concerns prevail regarding the metastatic potential of even small undiagnosed germ cell tumours. No consensus exists on optimal surveillance (short interval (<3 months) ultrasonography is generally adopted); histological sampling is a widespread alternative, involving inguinal delivery of the testis and excisional biopsy of the lesion, with preoperative marking or intraoperative ultrasonographic localization when necessary. Frozen section analysis in this context demonstrates excellent diagnostic accuracy. Histological results support that approximately two-thirds of marker-negative indeterminate solitary testicular lesions measuring ≤25 mm overall are benign. In summary, modern imaging detects many small indeterminate testicular lesions, of which the majority are benign. Awareness is growing of surveillance and organ-sparing diagnostic and treatment strategies with the aim of minimizing rates of overtreatment with radical orchidectomy.

Dosimetric effects of rotational errors for single isocenter multiple targets in HyperArc plans: A phantom and retrospective imaging analysis study.

PURPOSE: This study uses a phantom to investigate the dosimetric impact of rotational setup errors for Single Isocenter Multiple Targets (SIMT) HyperArc plans. Additionally, it evaluates intra-fractional rotational setup errors in patients treated with Encompass immobilization system. METHODS: The Varian HyperArc system (Varian Medical systems) was used to create plans targeting spherical PTVs with diameters of 5, 10, and 15 mm and with offsets of 1.3-5.3 cm from the isocenter. Dosimetric parameters, including mean and maximum dose, D99% and D95% were evaluated for various rotational setup errors ranging from 0.5° to 2° for the PTVs and certain CTVs created within PTVs. These rotational errors were applied in an order and direction that resulted in the maximum displacement of targets. The rotation was applied both uniformly around all three axes and individually around each axis. Furthermore, to link the findings to actual treatment scenarios, the intra-fractional rotational setup errors were obtained for stereotactic cranial patients treated with the Encompass system using CBCT images acquired during treatments. RESULTS: The maximum displacement of 2.7 mm was observed for targets located at 4.4 and 4.5 cm from the isocenter with rotational setup errors of 2°. The dose reduction for D99% values corresponding to this displacement were about 50%, 40%, and 30% for PTVs with diameters of 5, 10, and 15 mm, respectively. Both D99% and D95% showed a consistent trend of dose reduction across various rotational errors and PTV volumes. While the maximum dose remained consistent for different targets with various rotational errors, the mean dose decreased by approximately 25%, 12%, and 6% for PTVs with diameters of 5, 10, and 15 cm, respectively, with rotational errors of 2°. In addition, by analyzing CBCT images, the absolute mean rotational setup errors obtained during treatment with Encompass for pitch, roll, and yaw were 0.17° ± 0.13°, 0.11° ± 0.10°, and 0.12° ± 0.10° respectively. This data, combined with existing studies, suggest that a 0.5° rotational setup error is a safe choice to consider for calculating additional PTV margin to ensure adequate CTV coverage. Therefore, the assessment of maximum displacement and dosimetric parameters in this study, for a 0.5° rotational error, highlights the need for an additional 0.7 mm PTV margin for targets positioned at distances of 4.4 cm or greater from the isocenter. CONCLUSIONS: For SIMT Plans, a 0.5° rotational setup error is recommended as a basis for calculating additional PTV margins to ensure adequate CTV coverage when using the Encompass system.

An 8-year, single-centre experience of primary image-guided insertion of 'button' gastrostomy catheters: Technical and clinical results.

INTRODUCTION: 'Button' gastrostomy insertion is traditionally a two-step procedure with an initial longer gastrostomy tube inserted followed by placement of the shorter 'button' gastrostomy in 6 weeks when the track is mature. The aim of this study is to assess whether the placement of a Button gastrostomy de novo is a safe and effective method of radiologically inserted gastrostomy (RIG) insertion. METHODS: Using our Picture Archive and Communication System (PACS) and electronic patient charts we identified all patients who underwent primary 'button' gastrostomy over an 8-year period with at least a 1-year follow-up period. We evaluated technical success rate, indications for insertion, major and minor complications, 30-day mortality and the number of exchanges performed. RESULTS: Overall, 482 patients underwent a primary button RIG insertion during this period with an overall success rate of 97.1%. Indications for RIG insertion included neurological and neurosurgical disorders 236 (48.9%), head and neck malignancy 182 (37.8%), oesophageal malignancy 27 (5.6%) and other indications in 37 (7.7%). The mean age was 59.55 years (range 18-88 years) with 290 men (60.2%) and 192 women (39.8%). Major complications were recorded in 0.8% and minor complications in 1.7%. A 30-day mortality of 1% was identified (five patients), mortality was directly related to the RIG insertion in one patient (0.2%). A total of 65 exchanges/replacements took place over this period of time, with 33 (50.1%) due to 'inadvertent removal'. CONCLUSION: Primary button RIG insertion is a procedure that has a high success rate and low morbidity and mortality. We believe it is a safe and effective alternative to deliver enteral nutrition.

Transcatheter Embolization of the Inferior Epigastric Artery: Technique and Clinical Outcomes.

PURPOSE: Symptomatic rectus muscle sheath hematoma may be the result of bleeding originating from the inferior epigastric artery. We report the technique and the results from a series of consecutive patients treated by transcatheter embolization, evaluating both ipsilateral and contralateral retrograde approaches. METHODS: This was a retrospective study including patients with verified rectus muscle sheath hematoma as a result of active extravasation from the inferior epigastric artery referred for transcatheter embolization. Technical success, clinical success and major complications were calculated. In addition, minor complications, blood transfusions required after a technically successful embolization, length of stay, peri-procedural and 30-day mortality and overall survival at 6 months were obtained. All statistical analysis was performed using SPSS. RESULTS: Twenty-one patients (mean age = 59.67 ± 19.51 years old) were included. The cause of the bleeding in the vast majority was iatrogenic trauma (n = 12/21, 57.14%). Both contralateral (n = 12/21, 57.14%%) and ipsilateral (n = 9/21, 42.86%) retrograde approaches were used. Embolic materials included micro-coils (n = 13/20, 65%), microspheres (PVA) (n = 1/20, 5%), a combination of PVA and micro-coils (n = 5/20, 25%) and gel-foam (n = 1/20, 5%). Overall technical success was 95.2% (n = 20/21) while clinical success was achieved in all but one of the technically successful cases 95% (n = 19/20). One patient died peri-procedurally due to profound hemodynamic shock. There were no other major complications. Additional transfusion was necessary in 7 patients (n = 7/21, 33.33%). There was a significant increase in the hemoglobin levels after the embolization (7.03 ± 1.78 g/dL pre-procedure Vs 10.91 ± 1.7 g/dL post-procedure, p = 0.048). The median hospital stay was 8 days. The peri-procedure and 30-day mortality was 4.8% (n = 1/21) and 28.6% (n = 6/21) respectively. The 6-month survival was 61.9% (13/21). CONCLUSION: Percutaneous embolization of the inferior epigastric artery is a minimally invasive method with satisfactory results. Both ipsilateral and contralateral retrograde approaches are feasible.

Health Outcomes in Individuals with Problem and Pathological Gambling: An Analysis of the 2014 North Carolina Behavioral Risk Factor Survey System (BRFSS).

Problem and pathological gambling refers to subclinical and clinical levels of maladaptive gambling, respectively, and is associated with specific sociodemographic characteristics as well as a number of poor health outcomes. We examined such demographic, physical health, mental health, and health-related behaviors in a sample of 7045 low-risk gamblers and 244 problem/pathological gamblers. Participants completed the 2014 North Carolina Behavioral Risk Factor Surveillance System telephone survey. Using the National Opinion Research Center's Diagnostic Screen for Gambling Disorders-CLiP, participants were categorized as either "problem/pathological gamblers" or "low-risk gamblers." Problem/pathological gamblers were younger, more likely to be male, of ethnic minority status, unmarried, and of lower education than low-risk gamblers. No physical health variables differentiated the groups but problem/pathological gamblers reported experiencing significantly more adverse childhood experiences and engaging in significantly more tobacco and alcohol use compared to low-risk gamblers. Moreover, gender moderated relationships between gambling group and several of the alcohol use variables such that male problem/pathological gamblers exhibited greater alcohol use behavior than male low-risk gamblers but no such relationship was present in females. Overall, this study expands the current knowledgebase on disordered gambling and highlights the need to assess disordered gambling in public health samples. Clinical implications are discussed.

Percutaneous Radiofrequency Ablation Versus Robotic-Assisted Partial Nephrectomy for the Treatment of Small Renal Cell Carcinoma.

INTRODUCTION: The authors compared the oncologic outcomes of radiofrequency ablation (RFA) with robotic-assisted partial nephrectomy (RPN) for the treatment of T1 stage renal cell carcinoma (RCC). MATERIALS AND METHODS: This was a retrospective data analysis of a high-volume single tertiary centre. Patients were treated with RFA or RPN following multidisciplinary decision making. Only histologically proven RCCs were included. Baseline demographics were collected, and PADUA scores of tumour features were calculated to standardize baseline anatomy. Peri-operative complications, kidney function and oncological outcomes were compared. RESULTS: Sixty-three cases were included in each group. Baseline renal function was poorer in RFA, and 16/63 RFA patients had tumours in single kidneys compared to 1/63 RPN cases (p < 0.001). Length of stay was shorter in RFA (1 vs. 3 days, p < 0.0001). Post-procedure renal function decline at 30 days was significantly less in RFA [(-0.8) ± 9.6 vs. (-16.1) ± 19.5 mls/min/1.73 m2; p < 0.0001]. More minor complications were recorded in RPN (10/63 vs. 4/63, p = 0.15), but local recurrence was numerically higher in RFA (6/63 vs. 1/63, p = 0.11). Disease-free survival (DFS) was not significantly different (adjusted HR = 0.6, 95 % Cl 0.1-3.7; p = 0.60). Increasing tumour size was an independent predictor of local recurrence (adjusted HR = 1.7; 95 % Cl 1.1-2.6 per cm; p = 0.02). CONCLUSIONS: Both RPN and RFA offer very good oncological outcomes for the treatment of T1 RCC with low peri-operative morbidity and similar oncologic outcomes. RFA demonstrated fewer peri-operative complications and better preservation of renal function, whereas RPN had an insignificantly lower local recurrence rate. RFA should be offered alongside RPN for selected cases.

Gold over Branched Palladium Nanostructures for Photothermal Cancer Therapy.

Bimetallic nanostructures show exciting potential as materials for effective photothermal hyperthermia therapy. We report the seed-mediated synthesis of palladium-gold (Pd-Au) nanostructures containing multiple gold nanocrystals on highly branched palladium seeds. The nanostructures were synthesized via the addition of a gold precursor to a palladium seed solution in the presence of oleylamine, which acts as both a reducing and a stabilizing agent. The interaction and the electronic coupling between gold nanocrystals and between palladium and gold broadened and red-shifted the localized surface plasmon resonance absorption maximum of the gold nanocrystals into the near-infrared region, to give enhanced suitability for photothermal hyperthermia therapy. Pd-Au heterostructures irradiated with an 808 nm laser light caused destruction of HeLa cancer cells in vitro, as well as complete destruction of tumor xenographs in mouse models in vivo for effective photothermal hyperthermia.

How to choose a precursor for decomposition solution-phase synthesis: the case of iron nanoparticles.

The decomposition of organometallic compounds as precursors has revolutionized the synthesis of nanoparticles in solution. However, effective control of size and size distribution of iron nanoparticles has remained challenging due to the high reactivity of iron towards oxygen or oxygen-containing materials. Reported is a decomposition study that shows how metal to ligand bonding and symmetry of the compound can be manipulated to control the size and size distribution of iron nanoparticles in the 6-16 nm range. [Fe(η(5)-C6H3Me4)2] was found to be the optimal precursor with a narrow decomposition temperature range due to its symmetry and the low bond dissociation energy of the ligands from the Fe(ii) center. The precise control of nanoparticle size has enabled the tuning of magnetic properties from superparamagnetic to soft-ferromagnetic desirable for a wide range of biomedical applications.

Successful exclusion of a large bronchopleural fistula using an Amplatzer II vascular plug and glue embolization.

We report a case of a 63-year-old man with a complicated postsurgical bronchopleural fistula (BPF), which was treated with a minimally-invasive hybrid procedure using fluoroscopy, bronchoscopy, and thoracoscopy. A previous surgical attempt had failed to seal the pathologic tract. An Amplazter II vascular plug was successfully deployed into the BPF, followed by autologous blood and glue injection. An adjunctive endoscopically-guided glue embolization was deemed necessary. The 14-month clinical and imaging follow-up confirmed the successful exclusion of the BPF. No migration of the device was noted and the patient remained asymptomatic. The combined endoscopic and fluoroscopic guided management of a BPF using the Amplatzer II vascular plug and glue was proven safe and effective after mid-term follow-up.

Alterations in the rat serum proteome during liver injury from acetaminophen exposure.

Changes in the serum proteome were identified during early, fulminant, and recovery phases of liver injury from acetaminophen in the rat. Male F344 rats received a single, noninjury dose or a high, injury-producing dose of acetaminophen for evaluation at 6 to 120 h. Two-dimensional gel electrophoresis of immunodepleted serum separated approximately 800 stained proteins per sample from which differentially expressed proteins were identified by mass spectrometry. Serum alanine aminotransferase/aspartate aminotransferase levels and histopathology revealed the greatest liver damage at 24 and 48 h after high-dose acetaminophen corresponding to the time of greatest serum protein alterations. After 24 h, 68 serum proteins were significantly altered of which 23 proteins were increased by >5-fold and 20 proteins were newly present compared with controls. Only minimal changes in serum proteins were noted at the low dose without any histopathology. Of the 54 total protein isoforms identified by mass spectrometry, gene ontology processes for 38 unique serum proteins revealed involvement of acute phase response, coagulation, protein degradation, intermediary metabolism, and various carrier proteins. Elevated serum tumor necrosis factor-alpha from 24 to 48 h suggested a mild inflammatory response accompanied by increased antioxidant capability demonstrated by increased serum catalase activity. Antibody array and enzyme-linked immunosorbent assay analyses also showed elevation in the chemokine monocyte chemoattractant protein-1 and the metalloprotease inhibitor tissue inhibitor of metalloproteinases-1 during this same period of liver injury. This study demonstrates that serum proteome alterations probably reflect both liver damage and a concerted, complex response of the body for organ repair and recovery during acute hepatic injury.

Synchronous global assessment of gene and protein expression in colorectal cancer progression.

Well-established models of colorectal cancer progression are based on the idea that the disease evolves through a multistep process involving sequential genetic mutations, suggesting that progression through clinically defined stages should correlate with well-defined patterns of gene expression. The majority of studies to date, however, have assessed these processes one gene and one protein at a time. We report the first comprehensive assessment of both gene and protein expression performed in parallel across progressive stages of human colorectal neoplasia. Remarkably, despite the global nature of the gene expression assessment, very few genes could be linked with certainty to specific proteins through currently available annotations. Furthermore, the correlation of expression between identified genes and proteins was poor. Nevertheless, both produced expression signatures that differentiated normal mucosa and nonmalignant adenomas from each other and from the malignant carcinomas and both produced fairly consistent subclasses of the malignancies, suggesting that a molecular staging might be more appropriate provided that these profiles can be tied to clinical outcome. This is potentially important as clinical staging is widely used as a prognostic indicator and used in the decision to pursue adjuvant therapies.

Characterization of the human urinary proteome: a method for high-resolution display of urinary proteins on two-dimensional electrophoresis gels with a yield of nearly 1400 distinct protein spots.

The abundance profile of the human urinary proteome is known to change as a result of diseases or drug toxicities, particularly of those affecting the kidney and the urogenital tract. A consequence of such insults is the ability to identify proteins in urine, which may be useful as quantitative biomarkers. To succeed in discovering them, reproducible urine sample preparation methods and good protein resolution in two-dimensional electrophoresis (2-DE) gels for parallel semiquantitative protein measurements are desirable. Here, we describe a protein fractionation strategy enriching proteins of molecular masses (M(r)) lower than 30 kDa in a fraction separate from larger proteins. The fraction containing proteins with M(r)s higher than 30 kDa was subsequently subjected to immunoaffinity subtraction chromatography removing most of the highly abundant albumin and immunoglobulin G. Following 2-DE display, superior protein spot resolution was observed. Subsequent high-throughput mass spectrometry analysis of ca. 1400 distinct spots using matrix-assisted laser desorption/ionization-time of flight peptide mass fingerprinting and liquid chromatography-electrospray ionization tandem mass spectrometry lead to the successful identification of 30% of the proteins. As expected from high levels of post-translational modifications in most urinary proteins and the presence of proteolytic products, ca. 420 identified spots collapsed into 150 unique protein annotations. Only a third of the proteins identified in this study are described as classical plasma proteins in circulation, which are known to be relatively abundant in urine despite their retention to a large extent in the glomerular blood filtration process. As a proof of principle that our urinary proteome display effort holds promise for biomarker discovery, proteins isolated from the urine of a renal cell carcinoma patient were profiled prior to and after nephrectomy. Particularly, the decrease in abundance of the kininogen 2-DE gel spot train in urine after surgery was striking.