Baseline mitral regurgitation predicts outcome in patients referred for dobutamine stress echocardiography

Purpose: A number of parameters recorded during dobutamine stress echocardiography (DSE) are associated with worse outcome. However, the relative importance of baseline mitral regurgitation (MR) is unknown. The aim of this study was to assess the prevalence and associated implications of functional MR with long-term mortality in a large cohort of patients referred for DSE. Methods: 6745 patients (mean age 64.9±12.2 years) were studied. Demographic, baseline and peak DSE data were collected. All-cause mortality was retrospectively analyzed. DSE was successfully completed in all patients with no adverse outcomes. Results: MR was present in 1019 (15.1%) patients. During a mean follow up of 5.1±1.8 years, 1642 (24.3%) patients died and MR was significantly associated with increased all-cause mortality (p<0.001). With Kaplan-Meier analysis, survival was significantly worse for patients with moderate and severe MR (p<0.001). With multivariate Cox regression analysis, moderate and severe MR (HR 2.78; 95% CI 2.17 - 3.57; and HR 3.62; 95% CI 2.89 - 4.53, respectively) were independently associated with all-cause mortality. The addition of MR to C statistic models significantly improved discrimination. Conclusions: MR is associated with all-cause mortality and adds incremental prognostic information among patients referred for DSE. The presence of MR should be taken into account when evaluating the prognostic significance of DSE results

Predictive value of frozen-section analysis in the histological assessment of steatosis before liver transplantation.

Histological quality assessment of donated livers is a key factor for extending the cadaveric donor pool for liver transplantation. We retrospectively compared frozen-section analysis with routine histological permanent slides and the outcomes of grafts in liver biopsies from 294 candidate donors. The kappa concordance coefficient of agreement between frozen-section analysis and routine histological analysis was very good for macrosteatosis (kappa = 0.934), microsteatosis (kappa = 0.828), and total steatosis (kappa = 0.814). The correlation between the mean amounts of macrosteatosis, microsteatosis, and total steatosis in frozen and permanent sections was also significant (P 30% in 4 of 32 cases (12.5%) and in 23 of 62 cases (37.1%), respectively. The only 2 histological parameters of frozen sections able to predict graft dysfunction within 7 days of transplantation were macrosteatosis and total steatosis (P = 0.018 and P = 0.015, respectively, Mann-Whitney test). None of the other histopathological features evaluated in frozen sections, including portal inflammation, lobular necrosis, myointimal thickening, biliocyte regression, cholestasis, hepatocellular polymorphism, lipofuscin storage, and fibrous septa, were significantly correlated with the graft outcome. The frozen-section histological evaluation of biopsies from cadaveric liver donors is an accurate, time-effective, and predictive method for the assessment of graft suitability

Toward the definition of immunosuppressive regimens with antitumor activity.

Immunosuppressive therapies associated with organ transplantation produce an increased risk of cancer development. Malignancies are increased in transplant recipients because of the impaired immune system. Moreover, experimental data point to a tumor-promoting activity of various immunosuppressive agents. In this study, we compared the effects of 4 immunosuppressive agents with different mechanisms of action (cyclosporine, rapamycin, mycophenolic acid, and leflunomide) on the in vitro growth of various tumor cell lines and umbilical vein endothelial cells. To varying degrees rapamycin (10 ng/mL), mycophenolic acid (300 nmol/L), and leflunomide (30 micromol/L) highly inhibited the growth of human rhabdomyosarcoma, hepatocellular carcinoma, colorectal carcinoma, and endothelial cells. In contrast, cyclosporine (100 ng/mL) did not affect their growth. Our data suggest that regimens containing rapamycin, mycophenolic acid, or leflunomide, which have both immunosuppressive and antitumor activities, should be preferred in transplant recipients to minimize the risk of tumors

A histopathologic screening method for rational use of organs from prostate-specific antigen-positive multiorgan donors: the Italian Emilia-Romagna Region experience

Reduction of waiting-list length requires extension of the organ-donor pool to elderly males bearing an higher risk of prostate cancer incidence. Prostate-cancer screening in organ donors is currently based on prostate-specific antigen (PSA) assays (total PSA and free/total PSA). However, the specificity of these assays is restricted, limiting risk-benefit analysis. Since 2001, 33 multiorgan donor candidates presenting within Emilia-Romagna (Italy) with suspect ultrasonography or abnormal PSA values were submitted to a histopathologic screening method of the entire prostate based on extemporary frozen-section analysis (maximum 1 hour) of over 50% of the organ at 0.1 mm cutting levels. Extemporary diagnosis of adenocarcinoma was made in 12 (36%) cases, corresponding to 4.5% of the male candidates aged more than 50 years in the donor pool. In all cases, the final diagnosis confirmed the extemporary analysis. As well as maximizing safety, this novel approach should permit more refined risk-benefit analysi

Real time RT-PCR approach for the evaluation of ERBB2 overexpression in breast cancer archival samples: a comparative study with FISH, SISH, and immunohistochemistry.

We tested the reliability of real time reverse transcription polymerase chain reactions as an alternative method for the assessment of ERBB2 status in paraffin-embedded tissues of 83 patients with breast cancer and 20 non-neoplastic controls. PCR was also compared with the immunohistochemical (IHC) HercepTest score and with fluorescence (FISH) and silver (SISH) in-situ hybridization, in 42 selected cases. ERBB2 mRNA was overexpressed in 26/83 (31%) breast cancer samples, using a cutoff calculated as the mean value of the controls plus 3 SD or with the receiver operating curve. The PCR test showed a 96% sensitivity and a 100% specificity when compared with FISH, with an area under the receiver operating curve of 98.4%. Overexpression of ERBB2 at PCR was also significantly correlated with amplification in FISH (P<0.001, Mann-Whitney test) and in SISH (P<0.001, Mann-Whitney test), and with the IHC HercepTest scores 2 or 3 (P<0.001, Spearman rank correlation). FISH, SISH, and IHC were also compared with each other. ERBB2 amplification in FISH significantly correlated with that in SISH (P=0.002, chi test with a concordance of the 87%), but not with IHC HercepTest scores (P=0.214, chi test). Real time PCR is a reliable and cost-effective method for the assessment of ERBB2 status in archival breast cancer samples, compared with FISH. Its introduction in routine diagnostic pathology practice is feasible even if it requires amendments to the current clinical oncology protocols

OATP 1B1/1B3 expression in hepatocellular carcinomas treated with orthotopic liver transplantation.

The organic anion transporter peptides (OATP) 1B1 and 1B3 are hepatocytic-specific transporters determinant for the uptake of the contrast media Gd-EOB-DTPA during magnetic resonance, but variably lost in hepatocellular carcinoma (HCC). Here, we studied a series of HCCs from livers that underwent liver transplantation (OLT) and correlated the expression of OATP 1B1/1B3 with HCC morphological features and the expression of the biliary-type keratins K7 and K19, the latter previously correlated with a worse prognosis after OLT. Seventy-five HCCs from 69 OLT patients were evaluated by histology and immunohistochemistry with monoclonal antibodies against OATP 1B1/1B3, K7, and K19. Histopathological and immunohistochemical features were therefore compared to recipient follow-up data. Thirty-four (45%) HCCs were completely OATP-, and 18 (24%) showed positivity for K7 and/or K19. We observed a significant inverse correlation between OATP and K7/19 expression (P\u2009<\u20090.001): all OATP+ cases were K7/19-, while all K7+ and/or K19+ cases were OATP-. Sixteen cases were negative for all antibodies. No correlation was found between histopathological features and immunohistochemistry. Twenty-five recipients experienced HCC recurrence, and ten died from neoplastic recurrence. Neither OATP nor keratin expressions were correlated with HCC recurrence, while OATP negativity significantly correlated with HCC-related death after recurrence (P\u2009=\u20090.036). In conclusion, HCCs show a progressive loss in OATP immunoreactivity that correlates with the gain of a biliary phenotype. Although further studies are required to define these findings better, our results support the idea that OATP could be used together with K7/19 to identify a phenotypical "spectrum" in HCC progression

The pathologist and transplant safety: the histologic control

Non disponibil

Adenocarcinoma in Crohn's disease: the pathologist's experience in a tertiary referral centre of inflammatory bowel disease.

The aim of the present study is to describe the histological and mutational characteristics of a series of both large and small bowel adenocarcinomas in patients with Crohn's disease from a tertiary referral centre of inflammatory bowel disease. Bowel adenocarcinoma was diagnosed in 11 (1.7%) of 660 consecutive patients submitted to surgery for histologically proven Crohn's disease in 5 years. The following data were collected: tumour site, stage and grade, intracellular/extracellular mucin, lymphovascular invasion, immunohistochemistry for keratin 7, keratin 20 and CDX-2, mutation analyses of KRAS, B-RAF, PI3K and microsatellite instability. A strong predominance of male gender was observed (10/11). Four (36.4%) adenocarcinomas arose in the small bowel, five (45.4%) in the anus/rectum, and two (18.2%) in anastomosis. Furthermore, all cases of anorectal adenocarcinoma showed >50% of extracellular mucin, with associated KRAS mutations in three of five. No influence in cancer incidence by infliximab therapy was observed.Our series, one of the largest on the topic with immunomorphological and molecular deepening, showed that bowel adenocarcinomas in Crohn's disease have an aggressive behaviour and a strong predominance of extracellular mucin. In surgical specimens from Crohn's disease patients, mucinous-looking anal fistulas and ileal areas of adhesion/retraction should always be extensively sampled