Evaluating histologic grading systems and the expression of human cytomegalovirus in salivary gland mucoepidermoid carcinoma

Mucoepidermoid carcinoma (sMEC) is the most common salivary gland malignancy. Traditionally, these tumors are histologically graded using point-based systems. Accurate grading is needed to guide treatment; however, current systems are criticized as inconsistent and cumbersome. The finding of human cytomegalovirus (hCMV) as causative to the development of sMEC suggests viral activity may influence tumor grade. Twenty-three sMEC specimens were independently graded by two oral pathologists and one oral pathology resident using both the Armed Forces Institute of Pathology (AFIP) and Brandwein methods. Inter-observer agreement and predictive value to patient outcome were statistically analyzed. sMEC specimens were then immunohistochemically evaluated using antibodies to two different hCMV proteins. Higher inter-observer agreement was observed with the AFIP grading method. Statistical significance was not achieved to assess the predictive value of either grading system. Detection of hCMV was negative with one of the antibodies used, while the other was equivocal.Master of Scienc

Efficacy of hepatic transplantation in patients with primary sclerosing cholangitis

Controlled trials to assess the therapeutic benefit of orthotopic hepatic transplantation (OHTx) for primary sclerosing cholangitis (PSC) cannot be justified in view of improvement of patient survival after this operation since 1981. However, the actual patient survival with OHTx can be compared with the Mayo model estimated survival probabilities without OHTx. This model, which encompasses physical, biochemical and histopathologic parameters of PSC, was constructed from a study of 392 conservatively treated PSC patients at five international centers in England and North America. We compared the actual survival of 216 adult patients with the diagnosis of advanced PSC who underwent hepatic replacement with the expected survival estimated by the Mayo PSC natural history model, 'the simulated control technique.' OHTx was performed at the University of Pittsburgh and Mayo Medical Center between 5 December 1981 and 26 December 1990. The mean (plus or minus standard deviation) post-OHTx follow-up period was 34 ± 25 months (range of zero to 104 months). Before transplantation, biliary or portal hypertensive operation, or both, was performed upon 104 patients. At operation, the mean age of recipients was 42.1 ± 11.3 years and the mean value of total serum bilirubin was 13.3 ± 13.0 milligrams per deciliter. Extensive septal fibrosis and cirrhosis were histologically documented in 97 percent of the patients, with splenomegaly in 63 percent. Immunosuppressive therapy was based primarily on cyclosporin in 184 recipients and FK-506 in 32. Within six months, the Kaplan-Meier survival probability after OHTx (0.89) already was higher than predicted by the Mayo model (0.83). At five years, the Kaplan-Meier actual survival with OHTx was 0.73 compared with 0.28 expected Mayo model survival. The overall increased survival rate with transplantation was statistically significant (chi-square equals 126.6; p<0.001). At all risk stratifications, OHTx significantly improved survival with a p value of 0.031 (low risk), 0.001 (moderate risk) and <0.001 (high risk). Thus, OHTx is effective therapy for PSC. Disease gravity and unsuspected cholangiocarcinoma in the excised native liver adversely influenced short and long term survival rates after transplantation, respectively

Hepatic retransplantation in cholestatic liver disease: Impact of the interval to retransplantation on survival and resource utilization

The aim of our study was to quantitatively assess the impact of hepatic retransplantation on patient and graft survival and resource utilization. We studied patients undergoing hepatic retransplantation among 447 transplant recipients with primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) at 3 transplantation centers. Cox proportional hazards regression analysis was used for survival analysis. Measures of resource utilization included the duration of hospitalization, length of stay in the intensive care unit, and the duration of transplantation surgery. Forty-six (10.3%) patients received 2 or more grafts during the follow-up period (median, 2.8 years). Patients who underwent retransplantation had a 3.8-fold increase in the risk of death compared with those without retransplantation (P < .01). Retransplantation after an interval of greater than 30 days from the primary graft was associated with a 6.7-fold increase in the risk of death (P < .01). The survival following retransplantations performed 30 days or earlier was similar to primary transplantations. Resource utilization was higher in patients who underwent multiple consecutive transplantations, even after adjustment for the number of grafts during the hospitalization. Among cholestatic liver disease patients, poor survival following hepatic retransplantation is attributed to late retransplantations, namely those performed more than 30 days after the initial transplantation. While efforts must be made to improve the outcome following retransplantation, a more critical evaluation may be warranted for late retransplantation candidates

Effect of pretransplant serum creatinine on the survival benefit of liver transplantation

More candidates with creatinine levels ≥ 2 mg/dL have undergone liver transplantation (LT) since the implementation of Model for End-Stage Liver Disease (MELD)–based allocation. These candidates have higher posttransplant mortality. This study examined the effect of serum creatinine on survival benefit among candidates undergoing LT. Scientific Registry of Transplant Recipients data were analyzed for adult LT candidates listed between September 2001 and December 2006 (n = 38,899). The effect of serum creatinine on survival benefit (contrast between waitlist and post-LT mortality rates) was assessed by sequential stratification, an extension of Cox regression. At the same MELD score, serum creatinine was inversely associated with survival benefit within certain defined MELD categories. The survival benefit significantly decreased as creatinine increased for candidates with MELD scores of 15 to 17 or 24 to 40 at LT (MELD scores of 15-17, P < 0.0001; MELD scores of 24-40, P = 0.04). Renal replacement therapy at LT was also associated with significantly decreased LT benefit for patients with MELD scores of 21 to 23 ( P = 0.04) or 24 to 26 ( P = 0.01). In conclusion, serum creatinine at LT significantly affects survival benefit for patients with MELD scores of 15 to 17 or 24 to 40. Given the same MELD score, patients with higher creatinine levels receive less benefit on average, and the relative ranking of a large number of wait-listed candidates with MELD scores of 15 to 17 or 24 to 40 would be markedly affected if these findings were incorporated into the allocation policy. Liver Transpl 15:1808–1813, 2009. © 2009 AASLD.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/64545/1/21951_ftp.pd

Sangiovanni and Colombo

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Longitudinal assessment of mortality risk among candidates for liver transplantation

Liver allocation policy recently was modified to use the Model for End-Stage Liver Disease (MELD) for patients with chronic liver disease to stratify potential recipients according to risk for waitlist death. In this study, a retrospective cohort of 760 adult patients with chronic liver disease placed on the liver transplant waitlist between January 1995 and March 2001 and followed up for up to 74 months was studied to assess the ability of the MELD to predict mortality among waitlisted candidates and evaluate the prognostic importance of changes in MELD score over time. Serial MELD scores predicted waitlist mortality significantly better than baseline MELD scores or medical urgency status. Each unit of the 40-point MELD score was associated with a 22% increased risk for waitlist death ( P < .001), whereas medical urgency status was not a significant independent predictor. For any given MELD score, the magnitude and direction of change in MELD score during the previous 30 days (ΔMELD) was a significant independent mortality predictor. Patients with MELD score increases greater than 5 points over 30 days had a threefold greater waitlist mortality risk than those for whom MELD scores increased more gradually ( P < .0001). We conclude that mortality risk on the liver transplant waitlist is predicted more accurately by serial MELD score determinations than by medical urgency status or single MELD measurements. ΔMELD score over time reflects progression of liver disease and conveys important additional prognostic information that should be considered in the further evolution of national liver allocation policy.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/35282/1/500090102_ftp.pd

A prognostic model for the outcome of liver transplantation in patients with cholestatic liver disease

We studied the outcome of 436 patients with primary biliary cirrhosis (PBC) or primary sclerosing cholangitis (PSC) who underwent orthotopic liver transplant (OLT) at three major liver transplant centers. Univariate predictors of outcome included age, Karnofsky score, Child's class, Mayo risk score, United Network for Organ Sharing (UNOS) status, nutritional status, serum albumin, serum bilirubin, international normalized ratio, and the presence of ascites, encephalopathy, renal failure (serum creatinine > 2 mg/dL), and edema refractory to diuretics. Using these predictors, we developed a four variable mathematical prognostic model to help the liver transplant physician predict the following: 1) the amount of intraoperative blood loss; 2) the number of days in the intensive care unit (ICU); and 3) severe complications after surgery. The model uses age, renal failure, Child's class, and United Network for Organ Sharing status. This study is the first to model the outcome of liver transplant in patients with a specific etiology of chronic liver disease (PBC or PSC). The model may be used to help select patients for OLT and to plan the timing of their transplantation

A prospective study of the rate of progression in compensated, histologically advanced chronic hepatitis C

The incidence of liver disease progression among subjects with histologically advanced but compensated chronic hepatitis C is incomplete. The Hepatitis C Antiviral Long‐term Treatment against Cirrhosis Trial was a randomized study of 3.5 years of maintenance peginterferon treatment on liver disease progression among patients who had not cleared virus on peginterferon and ribavirin therapy. Patients were followed subsequently off therapy. Because maintenance peginterferon treatment did not alter liver disease progression, we analyzed treated and control patients together. Among 1,050 subjects (60% advanced fibrosis, 40% cirrhosis), we determined the rate of progression to cirrhosis over 4 years and of clinical outcomes over 8 years. Among patients with fibrosis, the incidence of cirrhosis was 9.9% per year. Six hundred seventy‐nine clinical outcomes occurred among 329 subjects. Initial clinical outcomes occurred more frequently among subjects with cirrhosis (7.5% per year) than subjects with fibrosis (3.3% per year) ( P < 0.0001). Child‐Turcotte‐Pugh (CTP) score ≥7 was the most common first outcome, followed by hepatocellular carcinoma. Following occurrence of a CTP score ≥7, the rate of subsequent events increased to 12.9% per year, including a death rate of 10% per year. Age and sex did not influence outcome rates. Baseline platelet count was a strong predictor of all clinical outcomes. During the 8 years of follow‐up, death or liver transplantation occurred among 12.2% of patients with advanced fibrosis and 31.5% of those with cirrhosis. Conclusion: Among patients with advanced hepatitis C who failed peginterferon and ribavirin therapy, the rate of liver‐related outcomes, including death and liver transplantation, is high, especially once the CTP score reaches at least 7. (H EPATOLOGY 2011)Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/87145/1/24370_ftp.pd

Evidence‐based development of liver allocation: a review

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/87029/1/j.1432-2277.2011.01274.x.pd