Outcomes of male patients attending the symptomatic breast unit: adherence to local and national imaging guidelines and effectiveness of clinical examination and imaging in detecting male breast cancer.

AIM: To review outcomes of male patients attending the breast unit, evaluate effectiveness of imaging and examination in detecting breast cancer and review adherence to guidelines for male breast imaging. MATERIALS AND METHODS: A retrospective review was undertaken of male patients attending Cambridge Breast Unit from 1 January 2015 to 31 December 2019. Patient electronic records and imaging were reviewed to establish demographics, clinical findings, imaging, biopsy, and pathology outcomes. RESULTS: Of 1,362 male patients attending the breast unit, 1,028 (75%) had imaging performed. Biopsy was performed in 41 men (3%), with 14 cancers diagnosed (1%). Clinical examination showed 42.7% sensitivity, 99.6% specificity, 54.6% positive predictive value (PPV) and 99.4% negative predictive value (NPV) for detection of cancer. Mammogram demonstrated 84.6% sensitivity, 99.4% specificity, 69.8% PPV, and 99.8% NPV for detection of malignancy. Ultrasound demonstrated 78.6% sensitivity, 98.9% specificity, 73.3% PPV and 99.2% NPV for detection of cancer. Forty-one percent of patients <40 years and 51% < 50 years were imaged, who according to local and Royal College of Radiologists (RCR) guidelines did not require imaging based on age and clinical score. CONCLUSION: Male patients account for a small proportion of referrals to the breast unit but generate significant workload. Imaging protocols, incorporating clinical score and age cut-off at 40 years remains robust for detecting malignancy. Clinician awareness of the imaging protocol, and close liaison with radiologists is essential to minimise additional radiology workload.

Unprovoked venous thromboembolism in women over 40: is screening for occult malignancy with mammography and abdominopelvic CT of benefit?

AIM: To determine imaging and pathological outcomes in cases of unprovoked venous thromboembolism (VTE) referred for mammogram. A secondary objective was to elucidate outcomes of abdominopelvic computed tomography (CT) imaging performed in this cohort. MATERIALS AND METHODS: A retrospective review of mammograms performed in cases of unprovoked VTE was undertaken from January 2016 to September 2019. Patient notes and imaging were reviewed to establish patient demographics, additional imaging required, biopsies performed, pathology findings, and eventual outcomes. Cases were reviewed to determine if concurrent CT abdomen/pelvis was performed to screen for malignancy. Outcomes of CT were recorded. RESULTS: One hundred and thirty-nine women attended for screening mammogram following unprovoked VTE during the study period. Mean patient age was 68 years (range 42-89 years). Fourteen women (10%) were recalled for further breast imaging, with two cases of confirmed malignancy (1.4%). Of the 139 women, 118 also underwent CT imaging, with 18 patients (15%) recalled for further investigations. Two (1.7%) cases of malignancy (lung and ovarian) were identified. CONCLUSION: A low cancer detection rate was demonstrated in women undergoing mammography or CT following unprovoked VTE. In addition, the high number of false-positive findings and need for additional investigations questions the value of screening in this setting. Based on these findings, Cambridge Breast Unit has ceased mammographic and abdominopelvic CT imaging in women with unprovoked VTE, anticipating the newly updated National Institute for Health and Care Excellence (NICE) guidelines.

The value of routine screening mammography in women aged 35-39 years in a symptomatic breast unit.

AIM: To determine the breast cancer detection rate at routine bilateral screening mammography in women aged 35-39 years attending a symptomatic breast clinic, in women of population-risk profile with a normal clinical examination. METHODS AND MATERIALS: A retrospective analysis of all mammograms performed on patients aged 35-39 years at St James's Hospital from 2011-2015 was carried out. Patients with moderate or high familial risk of breast cancer, personal breast cancer history or chest radiation, males, general practitioner (GP) and internal hospital referrals, and those with abnormal clinical examinations were excluded. Included women had "normal", "benign", or undocumented examination findings. Results of imaging, including ultrasound and histopathological results, were recorded. Information was extracted from the hospital's electronic record systems. RESULTS: Of 4,087 patients aged 35-39 who had bilateral mammograms from 2011-2015, 2,148 patients were excluded from analysis. Of 1,939 included women, four (0.21%) were diagnosed with breast cancer confirmed at histology based on mammographic findings: two invasive ductal carcinoma (8 and 2 mm) and two ductal carcinoma in situ (DCIS; 4.5 mm high-grade DCIS and 2 mm low-grade DCIS). Other histological findings included two B3, 46 B2, and three B1 lesions. Overall, 115 biopsies were performed in this cohort; 55 (47.8%) were attributable to mammographic screening, producing a biopsy rate of 2.8% due to mammography alone. CONCLUSION: Per 1,000 women screened, 2.1 cases of cancer were detected. This figure would be below accepted international thresholds to undertake screening mammography and raises radiation protection issues. Additionally, a large number of benign biopsies were undertaken, with likely resultant psychological impact. Further studies could inform national guidance.

Preclinical evaluation of radiation and systemic, RGD-targeted, adeno-associated virus phage-TNF gene therapy in a mouse model of spontaneously metastatic melanoma.

The incidence of melanoma in the United States continues to rise, with metastatic lesions notoriously recalcitrant to therapy. There are limited effective treatment options available and a great need for more effective therapies that can be rapidly integrated in the clinic. In this study, we demonstrate that the combination of RGD-targeted adeno-associated virus phage (RGD-AAVP-TNF) with hypofractionated radiation therapy results in synergistic inhibition of primary syngeneic B16 melanoma in a C57 mouse model. Furthermore, this combination appeared to modify the tumor microenvironment, resulting in decreased Tregs in the draining LN and increased tumor-associated macrophages within the primary tumor. Finally, there appeared to be a reduction in metastatic potential and a prolongation of overall survival in the combined treatment group. These results indicate the use of targeted TNF gene therapy vector with radiation treatment could be a valuable treatment option for patients with metastatic melanoma.

Determination of recall rates for assessment in high-risk women undergoing annual surveillance breast MRI.

AIM: To review all surveillance breast magnetic resonance imaging (MRI) examinations performed over a 6-year period at an Irish national centre to determine the recall rate, biopsy rate, and cancer-detection rates. MATERIALS AND METHODS: All breast MRI examinations performed for surveillance purposes in women at high risk of developing breast cancer between January 2009 and December 2014 were reviewed. The Breast Imaging-Reporting and Data System (BI-RADS) score for each MRI examination was determined, the type of additional imaging performed, and the method of biopsy, if performed, was recorded. Histology of the biopsy specimens was reviewed. RESULTS: Data for 715 women undergoing 1445 surveillance MRI examinations were identified. Of the examinations, 10.9% (157/1445) had MRI BI-RADS scores that required recall for further imaging and 6.3% (91/1445) required a biopsy. Recall rates were 14.2% (86/607) and 8.5% (71/838) in the prevalent and incident rounds, respectively. The overall cancer detection rate was 17 per 1000. CONCLUSION: The current UK guideline was not achieved and no studies to date have achieved the target of <7%. Aiming for this target could risk lowering the cancer-detection rate. The authors would suggest a target rate of <15% and <10% for the prevalent round and incident rounds, respectively.

Optical fiber poling by induction: analysis by 2D numerical modeling.

Since their first demonstration some 25 years ago, thermally poled silica fibers have been used to realize device functions such as electro-optic modulation, switching, polarization-entangled photons, and optical frequency conversion with a number of advantages over bulk free-space components. We have recently developed an innovative induction poling technique that could allow for the development of complex microstructured fiber geometries for highly efficient χ(2)-based device applications. To systematically implement these more advanced poled fiber designs, we report here the development of comprehensive numerical models of the induction poling mechanism itself via two-dimensional (2D) simulations of ion migration and space-charge region formation using finite element analysis.

Imaging features of poorly controlled congenital adrenal hyperplasia in adults.

Congenital adrenal hyperplasia (CAH) is a genetic autosomal recessive condition most frequently as a result of a mutation in the 21-hydroxylase enzyme gene. Patients with poorly controlled CAH can manifest characteristic imaging findings as a result of adrenocorticotrophic hormone stimulation or the effects of cortisol precursor excess on various target organs. We present a spectrum of imaging findings encountered in adult patients with poorly treated CAH, with an emphasis on radiological features and their clinical relevance.

Kerr nonlinear switching in a hybrid silica-silicon microspherical resonator.

A hybrid silicon-core, silica-clad microspherical resonator has been fabricated from the semiconductor core fiber platform. Linear and nonlinear characterization of the resonator properties have shown it to exhibit advantageous properties associated with both materials, with the low loss cladding supporting high quality (Q) factor whispering gallery modes which can be tuned through the nonlinear response of the crystalline core. By exploiting the large wavelength shift associated with the Kerr nonlinearity, we have demonstrated all-optical modulation of a weak probe on the timescale of the femtosecond pump pulse. This novel geometry offers a route to ultra-low loss, high-Q silica-based resonators with enhanced functionality.

Tunable continuous wave emission via phase-matched second harmonic generation in a ZnSe microcylindrical resonator.

Whispering gallery mode microresonators made from crystalline materials are of great interest for studies of low threshold nonlinear phenomena. Compared to amorphous materials, crystalline structures often exhibit desirable properties such as high indices of refraction, high nonlinearities, and large windows of transparency, making them ideal for use in frequency comb generation, microlasing and all-optical processing. In particular, crystalline materials can also possess a non-centrosymmetric structure which gives rise to the second order nonlinearity, necessary for three photon processes such as frequency doubling and parametric down-conversion. Here we report a novel route to fabricating crystalline zinc selenide microcylindrical resonators from our semiconductor fibre platform and demonstrate their use for tunable, low power continuous wave second harmonic generation. Visible red light is observed when pumped with a telecommunications band source by a process that is phase-matched between different higher order radial modes, possible due to the good spatial overlap between the pump and signal in the small volume resonator. By exploiting the geometrical flexibility offered by the fibre platform together with the ultra-wide 500-22000 nm transmission window of the ZnSe material, we expect these resonators to find use in applications ranging from spectroscopy to quantum information systems.

Post traumatic Fat Embolism in Common Femoral Vein on CT.

Fat embolism syndrome usually occurs following trauma where fat globules from long bone fractures produce pulmonary, cerebral or cutaneous effects. This case illustrates the presence of macroscopic fat in the right common femoral vein secondary to a long bone fracture. This finding is rare but should be looked for on cross-sectional imaging to allow early, aggressive treatment of fat embolism syndrome.

Optical fiber poling by induction.

Conventional thermal poling methods require direct physical contact to internal fiber electrodes. Here, we report an indirect electrostatic induction technique using electrically floating wires inside the fiber combined with external electric fields that can allow for facile poling of complex microstructured fibers (MOFs) of arbitrarily long lengths. In combination with our unique ability to use liquid gallium electrodes, inducing second-order nonlinearities inside otherwise difficult to access multi-core or multi-hole MOFs now becomes entirely feasible and practical. The formation of a permanent second-order nonlinearity is unequivocally demonstrated by realizing quasi-phase-matched frequency doublers using periodic UV erasure methods in the induction-poled fibers. The second-order susceptibility created inside the fiber is driven by the potential difference established between the floating electrodes, which we calculate via numerical simulations.

Four-wave mixing and octave-spanning supercontinuum generation in a small core hydrogenated amorphous silicon fiber pumped in the mid-infrared.

An octave-spanning supercontinuum is generated in a hydrogenated amorphous silicon core fiber when pumped in the mid-infrared regime. The broadband wavelength conversion which extends from the edge of the telecommunications band into the mid-infrared (1.64-3.37 µm) is generated by four-wave mixing (FWM) and subsequent pulse break-up, facilitated by the high material nonlinear figure of merit and the anomalous dispersion of the relatively small 1.7 µm diameter core fiber. The FWM sidebands and corresponding supercontinuum can be tuned through the pump parameters, and show good agreement with the predicted phase-matching curves for the fiber.

Outcomes of a patient recall following early failure of hip hemiarthroplasty.

BACKGROUND: Unexpected early loosening was noted in some patients who had bipolar hemiarthroplasties using aspecific combination of head and stem. AIM: A review of all patients who had received this implant combination was performed to establish whether there was a higher than expected failure rate and to identify those patients who had evidence of early loosening requiring further intervention or monitoring. METHODS: Theatre records were reviewed to identify those who had undergone bipolar hemiarthroplasty using these products. All surviving patients were contacted and offered an appointment at which they underwent clinical and radiological review. Following review, revision rates were compared to published Australian joint registry data. RESULTS: Of 247 eligible for recall, 139 attended for clinical and radiological review. The cumulative revision rate was 6.8 % at 4 years, with a mean time to revision of 26 months; however, there was a significantly higher revision rate of 12.1 % in those aged under 75 years at the time of surgery (p = 0.01). This is significantly higher than rates quoted for bipolar hemiarthroplasties in Australian joint registry data. CONCLUSION: Overall, higher than expected revision rates due to early loosening were seen for this product combination,especially in patients aged\75 years at the time of the initial surgery.

Ultrafast optical control using the Kerr nonlinearity in hydrogenated amorphous silicon microcylindrical resonators.

Microresonators are ideal systems for probing nonlinear phenomena at low thresholds due to their small mode volumes and high quality (Q) factors. As such, they have found use both for fundamental studies of light-matter interactions as well as for applications in areas ranging from telecommunications to medicine. In particular, semiconductor-based resonators with large Kerr nonlinearities have great potential for high speed, low power all-optical processing. Here we present experiments to characterize the size of the Kerr induced resonance wavelength shifting in a hydrogenated amorphous silicon resonator and demonstrate its potential for ultrafast all-optical modulation and switching. Large wavelength shifts are observed for low pump powers due to the high nonlinearity of the amorphous silicon material and the strong mode confinement in the microcylindrical resonator. The threshold energy for switching is less than a picojoule, representing a significant step towards advantageous low power silicon-based photonic technologies.

Nonlinear transmission properties of hydrogenated amorphous silicon core fibers towards the mid-infrared regime.

The nonlinear transmission properties of hydrogenated amorphous silicon (a-Si:H) core fibers are characterized from the near-infrared up to the edge of the mid-infrared regime. The results show that this material exhibits linear losses on the order of a few dB/cm, or less, over the entire wavelength range, decreasing down to a value of 0.29 dB/cm at 2.7µm, and negligible nonlinear losses beyond the two-photon absorption (TPA) edge ~ 1.7µm. By measuring the dispersion of the nonlinear Kerr and TPA parameters we have found that the nonlinear figure of merit (FOM(NL)) increases dramatically over this region, with FOM(NL) > 20 around 2µm and above. This characterization demonstrates the potential for a-Si:H fibers and waveguides to find use in nonlinear applications extending beyond telecoms and into the mid-infrared regime.

Ultrafast wavelength conversion via cross-phase modulation in hydrogenated amorphous silicon optical fibers.

We present a characterization of the spectral modulation and wavelength shifting induced via cross-phase modulation (XPM) in a hydrogenated amorphous silicon (a-Si:H) core optical fiber. Pump-probe experiments using picosecond and femtosecond signal pulses are shown to be in good agreement with numerical simulations of the coupled nonlinear propagation equations. The large 10nm red-shifts obtained with the femtosecond probe pulses are attributed to the high Kerr nonlinearity of the a-Si:H material. Extinction ratios as high as 12 dB are measured for the conversion process at telecommunications wavelengths, indicating the potential for high-speed nonlinear optical control in a-Si:H fibers and waveguides.