Based on our results, we urgently recommend for any histological report on excision of anal lesions to include a statement whether histological markers of HPV infection were detected. In individual cases, validation via HPV PCR must be considered.
Background
Cardiac surgery, especially when employing cardiopulmonary bypass (CPB) and deep hypothermic circulatory arrest (DHCA), is associated with systemic inflammatory responses that significantly affect morbidity and mortality. Intestinal perfusion abnormalities have been implicated in such responses, but the mechanisms linking local injury and systemic inflammation remain unclear. Intestinal mast cells (MC) are specialized immune cells that secrete various preformed effectors in response to cellular stress. We hypothesized that MCs are activated in a microenvironment shaped by intestinal ischemia/reperfusion (I/R), and investigated local and systemic consequences in a rat model of DHCA.
Methods and Results
Adult rats were cooled to 16-18°C on CPB before instituting DHCA for 45 minutes. Specimens were harvested following rewarming and 2 hours of recovery. Significant intestinal barrier disruption was found, together with macro- and microscopic evidence of I/R injury in ileum and colon but not in lungs or kidneys. Immunofluorescence and toluidine blue staining revealed MC hyperplasia and activation in the gut. Pretreatment with the MC stabilizer cromolyn sodium efficiently blocked MC degranulation and resulted in preserved intestinal morphology and barrier function following DHCA. Furthermore, cromolyn sodium treatment dramatically reduced intestinal neutrophil influx and systemic release of various proinflammatory cytokines.
Conclusions
Our data provides primary evidence that intestinal I/R is a leading pathophysiologic process in a rat model of DHCA and that intestinal injury and local and systemic inflammatory responses are critically dependent on MC activation. This identifies intestinal MCs as central players in DHCA-associated responses, and opens novel therapeutic possibilities for patients undergoing this procedure.
The type-specific persistence of oncogenic human papillomavirus (HPV) is considered to be the true precursor of cervical cancer at which the transcription of the viral oncogenes E6 and E7 is necessary for the malignant transformation and maintenance of the neoplastic state. In the present pilot study, a cohort of 66 women was investigated from a routine officebased screening population who had an index cytological result from normal to high-grade squamous intraepithelial lesions and who were also HPV-DNA positive for at least one of the following high-risk HPV types: HPV 16, 18, 31, 33 and 45 detected by MY09/MY11 consensus and GP5 + /6 + general primers, followed by sequencing. The expression of E6/E7 transcripts from the same HPV types was detected by the PreTect HPV-Proofer. Cervical status was checked 18 months after the mRNA test. The expression of E6/E7 mRNA was found in 58% of the cases showing a 97% concordance with the HPV-DNA types and a positive correlation with increasing cytological and histological grade. All HPV-mRNA positive cases were also positive for HPV DNA whereas 25 (38%) of the HPV-DNA positive cases did not express the respective mRNA. The diagnostic validity of the PreTect assay for detecting histologically-proven prevalent CIN3 lesions were: sensitivity 95%, specificity 55%, positive predictive value (PPV) 81% and negative predictive value (NPV) 86%. The prognostic power of the PreTect test for predicting cytological disease progression was as follows: 78% sensitivity, 60% specificity, 37% PPV and 90% NPV. In conclusion, our results showed that the detection of oncogenic HPV E6/E7 mRNA in cervical smears in a routine screening setting identifies prevalent CIN3 lesions with nearly 100% sensitivity and has a very high negative predictive value for disease progression during the natural course of HPV infection. Thus, testing for HPV oncogenic activity may be used as a clinically predictive marker to enhance the net effectiveness of screening and enable the prognostication of prevalent cervical lesions.
OBJECTIVE
To determine whether it is possible to stratify patients with superficial bladder cancer into low‐ and high‐risk groups for tumour recurrence/progression based on the chromosomal pattern detected by fluorescence in situ hybridization (FISH) in one urine cytology specimen used for follow‐up testing.
PATIENTS AND METHODS
Voided urine samples from 47 consecutive patients with urinary tract neoplasms (13 with no history of urothelial malignancy and 34 under follow‐up after complete transurethral resection of superficial urothelial carcinoma of the bladder) were evaluated by liquid‐based cytology (ThinPrep®, CYTYC Corp., Boxborough, MA, USA) and UroVysion FISH (Vysis‐Abbott, Downers Grove, IL).
RESULTS
Of the 34 patients under surveillance, the UroVysion test was negative in four, 17 had loss of 9p21 sequences either alone or combined with low‐frequency trisomy/ies or tetrasomy/ies of chromosomes 3, 7 and 17 in single cells (low‐risk FISH), and 13 also had complex aneusomies of the remaining chromosomes (high‐risk FISH). One of the four FISH‐negative neoplasms, four of the 17 low‐risk FISH cases and five of the 11 informative high‐risk FISH‐positive patients developed recurrence. Progression occurred only in patients with high‐risk FISH results, showing high‐frequency complex chromosomal polysomies (four of 11).
CONCLUSION
The results from this pilot study indicate that the UroVysion FISH test may help to individually assess the clinical behaviour of superficial bladder cancer, based on the chromosomal pattern of exfoliated tumour cells in follow‐up urinary cytology. It might be of use to identify those patients likely to progress at earlier and curable stages of disease, and lengthen the surveillance period in those with persistent or recurrent low‐risk disease.
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