Global microRNA profiling in favorable prognosis subgroups of cancer of unknown primary (CUP) demonstrates no significant expression differences with metastases of matched known primary tumors

No data exist on biologic differences between Cancer of unknown primary (CUP) and metastatic solid tumors of known primary site. We assigned a primary tissue of origin in 40 favorable CUP patients (A: serous peritoneal carcinomatosis n = 14, B: axillary adenocarcinoma n = 8, C: upper squamous cervical adenopathy n = 18) by means of a 64-microRNA assay. Subsequently, we profiled the expression of 733 microRNAs (miRs) in the CUP cases and compared results with metastases from 20 ovarian carcinomas, 10 breast adenocarcinomas, 20 squamous head neck or lung tumors. In the Peritoneal CUP versus Ovarian (Known Primary Metastases) KPM comparison, a total of 12 miR were significantly differentially expressed: higher than twofold expression difference in CUP was seen only for miR-513a-5p (3.7-fold upregulated) and miR-483-5p (2.5-fold upregulated), while miR-708 exhibited a twofold downregulation. In the Breast CUP versus Breast KPM comparison, only miR-29c that were downregulated in CUP by 2.7-fold satisfied the FDR threshold. miR-30e and miR-27b, downregulated in ovarian CUPs versus KPMs, were also non-significantly downregulated in breast CUP by 2.0- and 1.4-fold respectively. Six miRs, which belong to the 17–92 oncocluster showed a trend of upregulation in Breast CUP versus Breast KPM cases. A CUP signature remains elusive.     

Ultrasensitive Amplification Refractory Mutation System Real-Time PCR (ARMS RT-PCR) Assay for Detection of Minority Hepatitis B Virus-Resistant Strains in the Era of Personalized Medicine

Resistance to antiviral treatment for chronic hepatitis B virus (HBV) has been associated with mutations in the HBV polymerase region. This study aimed at developing an ultrasensitive method for quantifying viral populations with all major HBV resistance-associated mutations, combining the amplification refractory mutation system real-time PCR (ARMS RT-PCR) with a molecular beacon using a LightCycler. The discriminatory ability of this method, the ARMS RT-PCR with molecular beacon assay, was 0.01 to 0.25% for the different HBV resistance-associated mutations, as determined by laboratory-synthesized wild-type (WT) and mutant (Mut) target sequences. The assay showed 100% sensitivity for the detection of mutant variants A181V, T184A, and N236T in samples from 41 chronically HBV-infected patients under antiviral therapy who had developed resistance-associated mutations detected by direct PCR Sanger sequencing. The ratio of mutant to wild-type viral populations (the Mut/WT ratio) was >1% in 38 (63.3%) of 60 samples from chronically HBV-infected nucleos(t)ide analogue-naive patients; combinations of mutations were also detected in half of these samples. The ARMS RT-PCR with molecular beacon assay achieved high sensitivity and discriminatory ability compared to the gold standard of direct PCR Sanger sequencing in identifying resistant viral populations in chronically HBV-infected patients receiving antiviral therapy. Apart from the dominant clones, other quasispecies were also quantified. In samples from chronically HBV-infected nucleos(t)ide analogue-naive patients, the assay proved to be a useful tool in detecting minor variant populations before the initiation of the treatment. These observations need further evaluation with prospective studies before they can be implemented in daily practice.     

Risk assessment of atherosclerotic plaques based on global biomechanics

We present the results of a computational study of the entire left coronary system simulated both at Newtonian level and at red blood cell resolution for a sizeable number of physiological conditions. We analyze the cardiovascular implications of stenotic plaques and show that the standard clinical criterion for surgical or percutaneous intervention, based on the fractional flow reserve (FFR), is significantly affected by system-dependent, local hemodynamic factors. A refined version, based on the new notion of local FFR response to stenotic growth, and accounting for statistical uncertainties due to flow heterogeneity, is suggested and illustrated.     

Expression profiling of 21 biomolecules in locally advanced nasopharyngeal carcinomas of Caucasian patients

Background

Since scarce data exist on the pathogenesis of nasopharyngeal carcinoma in Caucasian patients, we attempted to elucidate the responsible molecular pathways in this patient population.

Methods

Formalin-fixed paraffin-embedded tumor tissue samples from 107 patients, diagnosed with locally-advanced nasopharyngeal carcinoma and treated with chemotherapy or chemo-radiotherapy, were analyzed by immunohistochemistry for the expression of the following proteins: E-cadherin, P-cadherin, Fascin-1, Cyclin D1, COX-2, EGFR, VEGF-A, VEGF-C, VEGFR-2, VEGFR-3, ERCC1, p53, p63, Ki67, MAPT, phospho-p44/42MAPK, PTEN, phospho-AKT, phospho-mTOR, and phospho-GSK-3β. EBER status was assessed by in situ hybridization. The majority of the cases were included in tissue microarray. All stains were performed and assessed centrally by two pathologists. The median follow-up time was 76.8 (42.3 – 99.2) months.

Results

Biomolecules expressed in >90% of cases were: p53, COX-2, P-cadherin, EBER, phospho-GSK-3β, and Fascin-1. WHO II+III tumors were more frequently EBER & PTEN positive and VEGF-A negative. Advanced age was significantly associated with positive phospho-GSK-3β and ERCC1 expression; male gender with positive phospho-AKT and phospho-p44/42MAPK; and worse performance status (1 or 2) with negative Ki67, ERCC1, PTEN, and phospho-mTOR expression. Earlier disease stage was closely associated with p63, MAPT, PTEN, and Cyclin D1 positivity. Univariate Cox regression analysis highlighted Cyclin D1 as a negative prognostic factor for disease-free survival (p=0.034) and EBER as a positive one for overall survival (p=0.048). In multivariate analysis, advanced age and stage, poor performance status, and positive ERCC1 emerged as predictors of worse disease-free and overall survival, as opposed to positive phospho-mTOR. Clustering analysis defined two protein-expression groups being predictive of better overall survival (p=0.043).

Conclusions

Our study is the first to examine the activation and interaction of established biomolecules and signaling pathways in Caucasian NPC patients in an effort to reveal new therapeutic targets.     

Physician level reporting of surgical and pathology performance indicators: a regional study to assess feasibility and impact on quality

Background

There is increased awareness that, to minimize variation in clinician practice and improve quality, performance reporting should be implemented at the provider level. This optimizes physician engagement and creates a sense of professional responsibility for quality and performance measurement at the individual and organizational levels.

Methods

Individual provider level reporting was implemented within a provincial health region involving 56 clinicians (general surgeons, surgical oncologists, urologists and pathologists). The 2 surgical pathology indicators chosen were colorectal cancer (CRC) lymph node retrieval rate and pT2 prostate cancer margin positivity rate. Surgical resections for all prostate and colorectal cancer performed between Jan. 1, 2011, and Mar. 30, 2012, were included. We used a pre- and postsurvey design to obtain physician perceptions and focus groups with program leadership to determine organizational impact.

Results

Survey results showed that respondents felt the data provided in the reports were valid (67%), consistent with expectations (70%), maintained confidentiality (80%) and were not used in a punitive manner (77%). During the study period the pT2 prostate margin positivity rate decreased from 57.1% to 27.5%. For the CRC lymph node retrieval rate indicator, high baseline performance was maintained.

Conclusion

We developed a robust process for providing physicians with confidential, individualized surgical and pathology quality indicator reports. Our results reinforce the importance of individual physician feedback as a strategy for improving and sustaining quality in surgical and diagnostic oncology.     

Breast cancer awareness among Greek women and potential determinants

Aim-Background

Despite the rise in the incidence of breast cancer (BC), a steady increase in the rate of survival has also been noted which can be directly attributed to early diagnosis, among others. Therefore, keeping women informed of the latest advances in BC treatment and prevention is crucial. The aim of this study is an attempt to quantify the level of awareness of Greek women on issues related to female BC prevention.

Methods

An online questionnaire of 24 items divided into three sections (sociodemographic, personal experience, as well as beliefs concerning BC prevention and screening) was completed and submitted anonymously by 2565 Greek women of all adult age groups and of various socioeconomic backgrounds.

Results

Only 42.8% of women used credible sources of information on health issues such as BC. Regular breast self-examination was adopted by one in three women. It emerged that 89% of women erroneously associated in vitro fertilization with an increased risk of BC, while half the women were unaware of the possibility of a false-negative result from breast screening. Low BC awareness was associated with low education, low economic status, younger age, single women from non-urban areas who did not have (or did not know if they had) a BC family history and who usually refrained from any kind of preventive actions.

Conclusions

The study revealed that there is a significant proportion of Greek women with a misperception or ignorance of BC prevention and the significance of early diagnosis. Since timely diagnosis is directly related to BC survival rate, specific actions (e.g. targeted educational interventions in specific subpopulations) should be assumed.

     

Sonography of the Scrotum

In this pictorial essay, we review and discuss the varying morphologic characteristics of scrotal appendages and calculi. Characteristic sonograms obtained from patients with coexisting hydrocele are presented, and recent literature is included. Hydrocele greatly facilitates the imaging of these intrascrotal structures, as it acts as a “water path”. On the one hand, torsion of a scrotal appendage should always be included in the differential diagnosis of acute scrotum, especially in children. On the other hand, scrotolithiasis may occasionally cause mild discomfort. As a consequence, and given the widespread use of sonography for the evaluation of both acute and chronic conditions of the scrotum, radiologists should be familiar with these entities.     

Incidence of needle‐tract seeding following prostate biopsy for suspected cancer: a review of the literature

With the widespread clinical use of prostate‐specific antigen (PSA), biopsy of the prostate has become one of the most commonly performed urological procedures. In general it is well tolerated, although there is some morbidity and risk of infection. In recent years, there have been increasing concerns that prostate biopsy may lead to tumour seeding along the needle tract. The aim of the present paper was to review the evidence on the prevalence of tumour seeding after prostate biopsy and to define the risk of this event in the context of current clinical practice. A PubMed literature search was conducted in January 2014 according to the Preferred Reporting Items for Systematic Reviews and Meta‐analysis (PRISMA) statement. Literature was examined with emphasis on the incidence of seeding, clinical presentation and on risk factors including type of needle used, transrectal vs transperineal approach, as well as tumour grade and stage. In all, 26 publications were identified reporting needle‐tract seeding after prostate biopsy. In all, 42 patients with needle‐tract seeding were identified. In most cases, seeding was reported after transperineal biopsy of the prostate, while nine cases occurred after transrectal biopsy. Based on the reviewed series the incidence of seeding appears to be <1%. The increase in the number of biopsies and cores taken at each biopsy over the years has not resulted in an increase in the reported cases of seeding. In conclusion, seeding along the needle track is a rare complication after prostate biopsy. Its actual incidence is presently difficult to quantify. It is reasonable to advise appropriate counselling and take measures to reduce this event where possible; however, we do not advocate avoidance of biopsies as the benefits of appropriate cancer diagnosis and management outweigh any potential risks from seeding.