Association of IgG4-related disease and systemic rheumatic disorders.

PURPOSE: Autoimmune disorders can occur together especially in genetically predisposed individuals. We here aimed to assess the occurrence of IgG4-related disease (IgG4-RD) in association with other systemic immune-mediated conditions. METHODS: We retrospectively analyzed the clinical records of patients with IgG4-RD followed at the IgG4-RD Clinic of San Raffaele Hospital (Milan, Italy) for pre-existing or concomitant immune-mediated disorders. IgG4-RD was diagnosed based on histological findings and on the 2011 Comprehensive Diagnostic criteria. Associated immune-mediated disorders were diagnosed based on available classification and/or diagnostic criteria. RESULTS: Two-hundred and thirty-four patients with a definitive diagnosis of IgG4-RD were included in this study. A pre-existing immune-mediated connective tissue disease was reported in 6/234 patients (3%): one case each of sarcoidosis, Takayasu arteritis (TA), eosinophilic granulomatosis with polyangitis (EGPA), and rheumatoid arthritis; and two cases of granulomatosis with polyangitis (GPA). Organs involved by IgG4-RD included the lungs, the pancreas, the peritoneum, lacrimal glands, meninges and orbits. Sarcoidosis, EGPA, and TA preceded the onset of IgG4-RD. GPA preceded IgG4-RD onset in one case and occurred simultaneously in the other case. Rheumatoid arthritis occurred together with IgG4-RD in one case. CONCLUSION: Our observation suggests that "secondary" IgG4-RD can present in the context of pre-existing systemic immune-mediated disorders and complicate systemic autoimmune diseases as well as chronic granulomatous conditions. Further studies are needed to define whether this peculiar clinical scenario is associated with different genetic backgrounds, pathological bases, and long-term outcomes.

PET/MRI for Staging the Axilla in Breast Cancer: Current Evidence and the Rationale for SNB vs. PET/MRI Trials.

Axillary surgery in breast cancer (BC) is no longer a therapeutic procedure but has become a purely staging procedure. The progressive improvement in imaging techniques has paved the way to the hypothesis that prognostic information on nodal status deriving from surgery could be obtained with an accurate diagnostic exam. Positron emission tomography/magnetic resonance imaging (PET/MRI) is a relatively new imaging tool and its role in breast cancer patients is still under investigation. We reviewed the available literature on PET/MRI in BC patients. This overview showed that PET/MRI yields a high diagnostic performance for the primary tumor and distant lesions of liver, brain and bone. In particular, the results of PET/MRI in staging the axilla are promising. This provided the rationale for two prospective comparative trials between axillary surgery and PET/MRI that could lead to a further de-escalation of surgical treatment of BC. • SNB vs. PET/MRI 1 trial compares PET/MRI and axillary surgery in staging the axilla of BC patients undergoing primary systemic therapy (PST). • SNB vs. PET/MRI 2 trial compares PET/MRI and sentinel node biopsy (SNB) in staging the axilla of early BC patients who are candidates for upfront surgery. Finally, these ongoing studies will help clarify the role of PET/MRI in BC and establish whether it represents a useful diagnostic tool that could guide, or ideally replace, axillary surgery in the future.

Synergic role of preoperative 18F-fluorodeoxyglucose PET and MRI parameters in predicting histopathological features of endometrial cancer.

BACKGROUND: The aim of the present study is to explore the correlation between PET and MRI parameters of primary tumour and clinicopathological features and to determine their synergic predictive role in patients with endometrial cancer candidate to surgery. METHODS: Retrospective study including 27 patients with endometrial cancer and preoperative 18F-fluorodeoxyglucose (18F-FDG)-PET and MRI scan. The following parameters, calculated on the primary tumour, were used for analysis: maximum standardized uptake value (SUVmax), SUVmean, metabolic tumour volume (MTV) and total lesion glycolysis (TLG) for PET scans; mean apparent diffusion coefficient (ADCmean) and volume index for MRI scans. FIGO stage, grade, histotype, lymphovascular space invasion (LVSI) and myometrial invasion were the considered clinicopathological features. RESULTS: MRI volume index was a good predictor for deep myometrial invasion [area under the curve (AUC) = 0.85; P = 0.003] and for LVSI (AUC = 0.74; P = 0.039). A cutoff value of 9.555 for MRI volume index was predictive for deep myometrial invasion (sensitivity = 84.6%; specificity = 76.9%); a cutoff of 12.165 was predictive for LVSI (sensitivity = 69.2%; specificity = 83.3%). A TLG cutoff value of 26.03 was predictive for deep myometrial invasion (sensitivity = 84.6%; specificity = 76.9%). A high-direct correlation was found with MRI volume index (rho = 0.722; P < 0.001); low-direct correlation with SUVmax (rho = 0.484; P = 0.012), SUVmean (rho = 0.47; P = 0.015) and TLG (rho = 0.482; P = 0.013) were identified. The SUVmax/ADCmean ratio showed a low-direct correlation with percentage of myometrial invasion (rho = 0.467; P = 0.016). CONCLUSION: Volume index, TLG and SUVmax/ADCmean ratio are associated with deep myometrial invasion. As myometrial invasion is the index used to predict lymph node involvement in endometrial cancer, the synergic use of these imaging parameters may be suggested to predict lymphnodal metastases.

Interreader variability in prostate MRI reporting using Prostate Imaging Reporting and Data System version 2.1.

OBJECTIVES: To evaluate the agreement among readers with different expertise in detecting suspicious lesions at prostate multiparametric MRI using Prostate Imaging Reporting and Data System (PI-RADS) version 2.1. METHODS: We evaluated 200 consecutive biopsy-naïve or previously negative biopsy men who underwent MRI for clinically suspected prostate cancer (PCa) between May and September 2017. Of them, 132 patients underwent prostate biopsy. Seven radiologists (four dedicated uro-radiologists and three non-dedicated abdominal radiologists) reviewed and scored all MRI examinations according to PI-RADS v2.1. Agreement on index lesion detection was evaluated with Conger's k coefficient, agreement coefficient 1 (AC1), percentage of agreement (PA), and indexes of specific positive and negative agreement. Clinical and radiological features that may influence variability were evaluated. RESULTS: Agreement in index lesion detection among all readers was substantial (AC1 0.738; 95% CI 0.695-0.782); dedicated radiologists showed higher agreement compared with non-dedicated readers. Clinical and radiological parameters that positively influenced agreement were PSA density ≥ 0.15 ng/mL/cc, pre-MRI high risk for PCa, positivity threshold of PI-RADS score 4 + 5, PZ lesions, homogeneous signal intensity of the PZ, and subjectively easy interpretation of MRI. Positive specific agreement was significantly higher among dedicated readers, up to 93.4% (95% CI 90.7-95.4) in patients harboring csPCa. Agreement on absence of lesions was excellent for both dedicated and non-dedicated readers (respectively 85.1% [95% CI 78.4-92.3] and 82.0% [95% CI 77.2-90.1]). CONCLUSIONS: Agreement on index lesion detection among radiologists of various experiences is substantial to excellent using PI-RADS v2.1. Concordance on absence of lesions is excellent across readers' experience. KEY POINTS: • Agreement on index lesion detection among radiologists of various experiences is substantial to excellent using PI-RADS v2.1. • Concordance between experienced readers is higher than between less-experienced readers. • Concordance on absence of lesions is excellent across readers' experience.

Systematic study of the effect of ultrasound gel on the performances of time-domain diffuse optics and diffuse correlation spectroscopy.

Recently, multimodal imaging has gained an increasing interest in medical applications thanks to the inherent combination of strengths of the different techniques. For example, diffuse optics is used to probe both the composition and the microstructure of highly diffusive media down to a depth of few centimeters, but its spatial resolution is intrinsically low. On the other hand, ultrasound imaging exhibits the higher spatial resolution of morphological imaging, but without providing solid constitutional information. Thus, the combination of diffuse optical imaging and ultrasound may improve the effectiveness of medical examinations, e.g. for screening or diagnosis of tumors. However, the presence of an ultrasound coupling gel between probe and tissue can impair diffuse optical measurements like diffuse optical spectroscopy and diffuse correlation spectroscopy, since it may provide a direct path for photons between source and detector. A systematic study on the effect of different ultrasound coupling fluids was performed on tissue-mimicking phantoms, confirming that a water-clear gel can produce detrimental effects on optical measurements when recovering absorption/reduced scattering coefficients from time-domain spectroscopy acquisitions as well as particle Brownian diffusion coefficient from diffuse correlation spectroscopy ones. On the other hand, we show the suitability for optical measurements of other types of diffusive fluids, also compatible with ultrasound imaging.

Deconstructing IgG4-related disease involvement of midline structures: Comparison to common mimickers.

OBJECTIVE: A series of destructive and tumefactive lesions of the midline structures have been recently added to the spectrum of IgG4-related disease (IgG4-RD). We examined the clinical, serological, endoscopic, radiological, and histological features that might be of utility in distinguishing IgG4-RD from other forms of inflammatory conditions with the potential to involve the sinonasal area and the oral cavity. METHODS: We studied 11 consecutive patients with erosive and/or tumefactive lesions of the midline structures referred to our tertiary care center. All patients underwent serum IgG4 measurement, flow cytometry for circulating plasmablast counts, nasal endoscopy, radiological studies, and histological evaluation of tissue specimens. The histological studies included immunostaining studies to assess the number of IgG4 + plasma cells/HPF for calculation of the IgG4+/IgG + plasma cell ratio. RESULTS: Five patients with granulomatosis with polyangiitis (GPA), three with cocaine-induced midline destructive lesions (CIMDL), and three with IgG4-RD were studied. We found no clinical, endoscopic, or radiological findings specific for IgG4-RD. Increased serum IgG4 and plasmablasts levels were not specific for IgG4-RD. Rather, all 11 patients had elevated blood plasmablast concentrations, and several patients with GPA and CIMDL had elevated serum IgG4 levels. Storiform fibrosis and an IgG4+/IgG + plasma cell ratio >20% on histological examination, however, were observed only in patients with IgG4-RD. CONCLUSIONS: Histological examination of bioptic samples from the sinonasal area and oral cavity represents the mainstay for the diagnosis of IgG4-RD involvement of the midline structures.

Tailored breast cancer screening program with microdose mammography, US, and MR Imaging: short-term results of a pilot study in 40-49-year-old women.

PURPOSE: To evaluate the feasibility, performance, and cost of a breast cancer screening program aimed at 40-49-year-old women and tailored to their risk profile with supplemental ultrasonography (US) and magnetic resonance (MR) imaging. MATERIALS AND METHODS: The institutional review board approved this study, and informed written consent was obtained. A total of 3017 40-49-year-old women were invited to participate. The screening program was tailored to lifetime risk (Gail test) and mammographic density (according to Breast Imaging Reporting and Data Systems [BI-RADS] criteria) with supplemental US or MR imaging and bilateral two-view microdose mammography. The indicators suggested by European guidelines, US incremental cancer detection rate (CDR), and estimated costs were evaluated. RESULTS: A total of 1666 women (67.5% participation rate) were recruited. The average lifetime risk of breast cancer was 11.6%, and nine women had a high risk of breast cancer; 917 women (55.0%) had a high density score (BI-RADS density category 3 or 4). The average glandular dose for screening examinations was 1.49 mGy. Screening US was performed in 835 study participants (50.1%), mostly due to high breast density (800 of 1666 women [48.0%]). Screening MR imaging was performed in nine women (0.5%) at high risk for breast cancer. Breast cancer was diagnosed in 14 women (8.4 cases per 1000 women). Twelve diagnoses were made with microdose mammography, and two were made with supplemental US in dense breasts (2.4 cases per 1000 women). All patients were submitted for surgery, and 10 underwent breast-conserving surgery. The sentinel lymph node was evaluated in 11 patients, resulting in negative findings in six. Pathologic analysis resulted in the diagnosis of four ductal carcinomas in situ and 10 invasive carcinomas (five at stage I). CONCLUSION: A tailored breast cancer screening program in 40-49-year-old women yielded a greater-than-expected number of cancers, most of which were low-stage disease.

Intein-mediated expression of cecropin in escherichia coli

Different strategies have been used to overcome the difficulties to produce antimicrobial peptides. Here we used Intein Mediated Purification with an Affinity Chitin-binding Tag (IMPACT-System, New England Biolabs) for the expression of the antimicrobial peptide cecropin to reduce its sensitivity to intracellular proteases and use its inducible self-cleaving capability to remove the carrier. Cecropin was cloned into suitable expression vector pTYB11, and expression induced by IPTG in Escherichia coli ER2566. The use of 22ºC induction allowed the expression of cecropin with its intein carrier in soluble form. Cell extracts were purified by chitin affinity chromatography and intein-mediated splicing of the target protein was achieved by thiol addition, obtaining a final yield of 2.5 mg cecropin/l. Cecropin cleaved from the intein had its proper biologically active form, showing a micromolar antimicrobial activity against Vibrio ordalii, Vibrio alginolyticus and Escherichia coli.