Donor-derived Cell-free DNA Evaluation in Pediatric Heart Transplant Recipients: A Single-center 12-mo Experience.

Background: Endomyocardial biopsy (EMB) is considered the gold-standard method to diagnose rejection after heart transplantation. However, the many disadvantages and potential complications of this test restrict its routine application, particularly in pediatric patients. Donor-derived cell-free DNA (dd-cfDNA), released by the transplanted heart as result of cellular injury, is emerging as a biomarker of tissue damage involved in ischemia/reperfusion injury and posttransplant rejection. In the present study, we systematically evaluated dd-cfDNA levels in pediatric heart transplant patients coming for follow-up visits to our clinic for 12 mo, with the aim of determining whether dd-cfDNA monitoring could be efficiently applied and integrated into the posttransplant management of rejection in pediatric recipients. Methods: Twenty-nine patients were enrolled, and cfDNA was obtained from 158 blood samples collected during posttransplant follow-up. dd-cfDNA% was determined with a droplet-digital polymerase chain reaction assay. EMB scores, donor-specific antibody measurements, and distress marker quantification were correlated with dd-cfDNA, together with echocardiogram information. Results: The percentage of dd-cfDNA increased when EMBs scored positive for rejection (P = 0.0002) and donor-specific antibodies were present (P = 0.0010). N-terminal pro-B-type natriuretic peptide and high-sensitive troponin I elevation were significantly associated with dd-cfDNA release (P = 0.02 and P < 0.0001, respectively), as were reduced isovolumetric relaxation time (P = 0.0031), signs of heart failure (P = 0.0018), and treatment for rejection (P = 0.0017). By determining a positive threshold for rejection at 0.55%, the test had a negative predictive value maximized at 100%. Conclusions: Collectively, results indicate that dd-cfDNA monitoring has a high negative prognostic value, suggesting that in heart transplanted children with dd-cfDNA levels of <0.55% threshold, protocol EMBs may be postponed.

Oral potentially malignant lesions: first-level micro-histological diagnosis from tissue fragments sampled in liquid-based diagnostic cytology.

BACKGROUND: Scalpel biopsy may under-diagnose oral dysplasia/carcinoma in potentially malignant lesions (PMLs) because samples represent only one or a few sites. It is possible that small tissue specimens obtained from over the whole area of PMLs, by scraping with a dermatological curette, could be treated histologically and used as 'micro' biopsies. This study values the accuracy of micro-biopsies in the detection of dysplasia/carcinoma in oral PMLs. METHODS: A prospective study was carried out on 164 patients with PMLs, with both scalpel and micro-biopsies, for the presence of dysplasia/carcinoma. The most severe diagnosis (obtained by either method) was used as the reference standard. The presence/absence of the basement membrane zone (BMZ) in the micro-biopsy specimens correlated with the site, the clinical features of the PMLs and the operator. RESULTS: Micro-biopsy gave six of 164 (3.66%) inadequate specimens. Of 158 of 164 adequate samples, dysplasia/carcinoma was diagnosed in 85 of 158 cases; micro-biopsy diagnosis was in agreement with scalpel biopsy in 144 of 158 (91.14%) cases and showed a better sensitivity than did scalpel biopsy (97.65% vs. 85.88%), corresponding to two of 158 false-negative cases by micro-biopsy vs. 12 of 158 by scalpel biopsy. The BMZ was observed in 110 of 158 (69.62%) of all micro-biopsies and had no relationship with the sampling site, the clinical features of the PMLs or the operator. CONCLUSIONS: The negative predictive value (97.33%) suggests that micro-biopsy may well be an effective first-level diagnostic procedure for PMLs (especially in follow-ups and multiple lesions); moreover, in carcinoma (17% of cases) a definitive diagnosis could be made without further investigation.

The attribution of lung cancers to asbestos exposure: a pathologic study of 924 unselected cases.

We studied a series of 924 nonselected surgical cases of lung carcinoma (without occupational history in clinical records) by histologic examination and light microscopic determination of asbestos body (AB) concentration to determine cancers attributable to asbestos exposure. Lower lobes showed higher concentrations, but no significant associations were recorded between concentrations and histologic type of the lung carcinomas. Histologic asbestosis was demonstrated in 56 cases considered definitely asbestos-related. In 12 of them, the demonstration of asbestosis was attained only after repeated examination of additional sections, suggested by thefinding of more than 1,000 ABs per gram of dry weight (gdw), an indicator of occupational asbestos exposure. In the 56 cases, the media

Microsurgical "testis-sparing" surgery for nonpalpable hypoechoic testicular lesions.

OBJECTIVES: With the increased use of trans-scrotal ultrasonography, the unexpected detection of nonpalpable hypoechoic testicular lesions has become more frequent. The different approaches vary from radical orchiectomy to simple ultrasound follow-up, but definitive guidelines do not yet exist about the management of these lesions. We report our series of patients with hypoechoic testicular lesions who underwent surgical exploration with the aid of an operating microscope. METHODS: A total of 7 patients were considered for microsurgical exploration of a nonpalpable hypoechoic testicular lesion from April 2003 to June 2005. The hospital records and ultrasound and operative reports were reviewed retrospectively. RESULTS: The side of the lesion was the left testis in 4 patients and the right testis in 3. The mean size of the hypoechoic area was 5.7 +/- 4.6 mm (range 2.5 to 16). The microsurgical technique allowed us to identify and successfully excise the lesion in all patients. Intraoperative frozen section examination revealed a benign lesion in 6 cases and testicular intraepithelial neoplasia in 1. The patient with testicular intraepithelial neoplasia underwent radical orchiectomy. The definitive histologic analysis always confirmed the frozen section examination report. The patients were evaluated clinically and by ultrasonography for a mean follow-up of 15 months. No complications occurred. CONCLUSIONS: Microsurgical exploration of the testis combined with frozen section examination represents a safe, effective, and reliable technique for evaluation of nonpalpable hypoechoic testicular lesions. This approach has significant advantages and should be considered in particular for patients with a solitary testis or presenting with bilateral lesions and wishing to father a child.