Interlaboratory reproducibility and proficiency testing within the human papillomavirus cervical cancer screening program in Catalonia, Spain.

In Catalonia, a screening protocol for cervical cancer, including human papillomavirus (HPV) DNA testing using the Digene Hybrid Capture 2 (HC2) assay, was implemented in 2006. In order to monitor interlaboratory reproducibility, a proficiency testing (PT) survey of the HPV samples was launched in 2008. The aim of this study was to explore the repeatability of the HC2 assay's performance. Participating laboratories provided 20 samples annually, 5 randomly chosen samples from each of the following relative light unit (RLU) intervals: <0.5, 0.5 to 0.99, 1 to 9.99, and ≥10. Kappa statistics were used to determine the agreement levels between the original and the PT readings. The nature and origin of the discrepant results were calculated by bootstrapping. A total of 946 specimens were retested. The kappa values were 0.91 for positive/negative categorical classification and 0.79 for the four RLU intervals studied. Sample retesting yielded systematically lower RLU values than the original test (P<0.005), independently of the time elapsed between the two determinations (median, 53 days), possibly due to freeze-thaw cycles. The probability for a sample to show clinically discrepant results upon retesting was a function of the RLU value; samples with RLU values in the 0.5 to 5 interval showed 10.80% probability to yield discrepant results (95% confidence interval [CI], 7.86 to 14.33) compared to 0.85% probability for samples outside this interval (95% CI, 0.17 to 1.69). Globally, the HC2 assay shows high interlaboratory concordance. We have identified differential confidence thresholds and suggested the guidelines for interlaboratory PT in the future, as analytical quality assessment of HPV DNA detection remains a central component of the screening program for cervical cancer prevention.

Molecular profiling related to poor prognosis in thyroid carcinoma. Combining gene expression data and biological information.

Undifferentiated and poorly differentiated thyroid tumors are responsible for more than half of thyroid cancer patient deaths in spite of their low incidence. Conventional treatments do not obtain substantial benefits, and the lack of alternative approaches limits patient survival. Additionally, the absence of prognostic markers for well-differentiated tumors complicates patient-specific treatments and favors the progression of recurrent forms. In order to recognize the molecular basis involved in tumor dedifferentiation and identify potential markers for thyroid cancer prognosis prediction, we analysed the expression profile of 44 thyroid primary tumors with different degrees of dedifferentiation and aggressiveness using cDNA microarrays. Transcriptome comparison of dedifferentiated and well-differentiated thyroid tumors identified 1031 genes with >2-fold difference in absolute values and false discovery rate of <0.15. According to known molecular interaction and reaction networks, the products of these genes were mainly clustered in the MAPkinase signaling pathway, the TGF-beta signaling pathway, focal adhesion and cell motility, activation of actin polymerization and cell cycle. An exhaustive search in several databases allowed us to identify various members of the matrix metalloproteinase, melanoma antigen A and collagen gene families within the upregulated gene set. We also identified a prognosis classifier comprising just 30 transcripts with an overall accuracy of 95%. These findings may clarify the molecular mechanisms involved in thyroid tumor dedifferentiation and provide a potential prognosis predictor as well as targets for new therapies.

Comparison of cytospat and pipelle endometrial biopsy instruments.

OBJECTIVE: To compare two endometrial biopsy techniques, based on the quality of material obtained, cost effectiveness, and pain during the procedure. STUDY DESIGN: A single blind, randomized prospective study. RESULTS: A total of 365 women with peri/postmenopausal bleeding were randomized into two groups: 174 biopsied cytospat (C) and 191 biopsied with pipelle (P). Both procedures were then followed by either dilatation and curettage (D&C) or hysterectomy. Pain was evaluated in 379 patients, with the result being better tolerance for P vs. C (3.55 vs. 4.06, P = 0.07). With C, the sensitivity in histological evaluation was 82% for benign endometrium, 60% for endometrial hyperplasia and 60% for corpus uterine neoplasia as compared to the D&C and hysterectomy material. With P the sensitivity was 84, 71 and 60%, respectively for the three diagnoses, as compared to the D&C and hysterectomy material. Insufficient tissue for pathologic evaluation was present in 24% of C, 25% of P and 9.8% of D&C samples. CONCLUSIONS: Cost effectiveness for pipelle is slightly higher than for Cytospat.

Gastric ulcer perforation into the heart.

Penetration of the pericardium and heart is a very rare complication of benign peptic ulcer. The case is reported here of a 76-year-old woman with advanced senile dementia, who was admitted due to melena. Endoscopy revealed a large gastric ulcer located in a giant hiatal hernia. The ulcer base was protruding and strongly pulsatile, and seemed to be mobile and free in relation to the ulcer margins. This effect was particularly obvious during the pulsatile movements. Endoscopic findings suggested ulcer perforation to the pericardium. The patient's relatives denied consent to surgery. She was therefore treated with conservative measures, including parenteral nutrition, ranitidine, and antibiotics. The patient remained in a relatively stable condition, and she was discharged three weeks later. One month later, however, she was admitted with massive bleeding and hypovolemic shock. In spite of resuscitation measures, she died. The autopsy study showed a gastric ulcer penetrating through the pericardium and myocardium into the left ventricle.

Superficial esophageal carcinoma: a report of 12 cases.

Twelve cases of superficial carcinoma of the esophagus, representing 4.9% of patients with carcinoma of the esophagus, were evaluated. All the patients were male smokers who drank alcohol excessively. The main clinical features were dysphagia, asthenia, anorexia, and weight loss. Most of the lesions were elevated and all endoscopic biopsies were positive for cancer. Half of the cases showed invasion of the submucosa; the remainder involved mucosa only. Ten patients are alive and free of metastatic disease.