Incidence and prognosis of different types of functional renal failure in cirrhotic patients with ascites.

BACKGROUND & AIMS: Hepatorenal syndrome is a well-characterized type of terminal renal failure that occurs in patients with cirrhosis with ascites. Information about other types of functional renal failure in these patients is scarce. We assessed the incidence and prognosis of different types of functional renal failure in cirrhotic patients with ascites and investigated prognostic factors for these disorders. METHODS: Consecutive cirrhotic patients (n = 263) were followed for 41 +/- 3 months after their first incidence of ascites. Three types of functional renal failure were considered: pre-renal failure (when renal failure was associated with a depletion of intravascular volume), renal failure induced by infection that did not result in hepatorenal syndrome, and hepatorenal syndrome. RESULTS: During the follow-up period, 129 (49%) patients developed some type of functional renal failure. The most frequent was pre-renal failure (27.4%), followed by renal failure induced by infection (14.1%), and then hepatorenal syndrome (7.6%). The 1-year probability of developing the first episode of any functional renal failure was 23.6%. The independent predictors of functional renal failure development were baseline age, Child-Pugh score, and serum creatinine. Although the 1-year probability of survival was 91% in patients without renal failure, it decreased to 46.9% in those patients who developed any functional renal failure (P = .0001). CONCLUSIONS: Approximately 50% of the cirrhotic patients with ascites developed some type of functional renal failure during the follow-up period; renal failure was associated with worse prognosis. Efforts should be made to prevent renal failure in cirrhotic patients with ascites.

A prospective, multicenter, population-based study of BRAF mutational analysis for Lynch syndrome screening.

BACKGROUND & AIMS: Mismatch repair (MMR) deficiencies are the hallmark of tumors arising in Lynch syndrome, however, in approximately 15% of sporadic colorectal cancers (CRC) these deficiencies most often are associated with somatic methylation of the MMR gene MLH1. Recently, an oncogenic mutation in the BRAF gene has been involved in sporadic CRC showing MMR deficiencies as a result of MLH1 promoter methylation. The aim of this study was to evaluate the contribution of BRAF V600E mutation analysis in the identification of MSH2/MLH1 gene mutation carriers in newly diagnosed CRC patients. METHODS: BRAF V600E mutation was analyzed in CRC patients with MMR deficiencies (microsatellite instability and/or lack of MLH1/MSH2 protein expression) in the EPICOLON population-based study. The effectiveness and efficiency of different strategies were evaluated with respect to the presence of MSH2/MLH1 germline mutations. RESULTS: MMR deficiencies were detected in 119 of the 1222 CRC patients with tumors showing either microsatellite instability (n = 111) or loss of protein expression (n = 81). BRAF mutation was detected in 22 (18.5%) of the patients. None of the patients with unambiguous germline mutation had BRAF mutation. Regardless of the strategy used to identify MSH2/MLH1 gene carriers, the introduction of BRAF analysis in these patients slightly improves their effectiveness. The introduction of BRAF mutation analysis as a step before germline genetic testing in patients with MMR deficiencies achieved a significant reduction in costs per mutation detected. CONCLUSIONS: Detection of BRAF V600E mutation could simplify and improve the cost effectiveness of genetic testing for hereditary nonpolyposis colorectal cancer, especially in patients whose family history is incomplete or unknown.

Detection of metachronous neoplasms in colorectal cancer patients: identification of risk factors.

PURPOSE: Patients with colorectal cancer have a high risk of developing metachronous neoplasms. Identification of predictive factors associated with such conditions would allow individualized follow-up strategies in these patients. This study was designed to identify individual and familial factors associated with the development of metachronous colorectal neoplasms in patients with colorectal cancer. METHODS: In the context of a prospective, multicenter, general population-based study-the EPICOLON project-all patients with colorectal cancer attended in ten Spanish hospitals during a one-year period were included. Patients with familial adenomatous polyposis or inflammatory bowel disease were excluded. All patients were monitored by colonoscopy within two years of the diagnoses. Demographic, clinical, pathologic, molecular (microsatellite instability status and immunohistochemistry for MSH2 and MLH1), and familial characteristics (fulfillment of Amsterdam I or II criteria, and revised Bethesda guidelines) were analyzed. RESULTS: A total of 353 patients were included in the study. At two years of follow-up, colonoscopy revealed the presence of adenomas in 89 (25 percent) patients and colorectal cancer in 14 (3.9 percent) patients, in 7 cases restricted to anastomosis. Univariate analysis demonstrated that development of metachronous neoplasm (adenoma or colorectal cancer) was associated with personal history of previous colorectal cancer (odds ratio, 5.58; 95 percent confidence interval, 1.01-31.01), and presence of previous or synchronous adenomas (odds ratio, 1.77; 95 percent confidence interval, 1.21-3.17). Although nonstatistical significance was achieved, metachronisms were associated with gender (P<0.09) and differentiation degree (P<0.08). Multivariate analysis identified previous or synchronous adenomas (odds ratio, 1.98; 95 percent confidence interval, 1.16-3.38) as independent predictive factor. Neither presence of tumor DNA microsatellite instability nor family history correlated with the presence of metachronous neoplasms. CONCLUSIONS: Patients with previous or synchronous colorectal adenoma have an increased risk of developing metachronous colorectal neoplasms. Accordingly, this subgroup of patients may benefit from specific surveillance strategies.

Natural history of patients hospitalized for management of cirrhotic ascites.

BACKGROUND & AIMS: Since the International Ascites Club published the diagnostic criteria of refractory ascites (RA) and hepatorenal syndrome (HRS), there have been few studies assessing the natural history of ascites. The aims of this study were to define the natural history of cirrhotic ascites and to identify prognostic factors for dilutional hyponatremia (DH), RA, HRS, and survival. METHODS: Two hundred sixty-three consecutive cirrhotic patients were followed for 40.9 +/- 2.6 months after their first significant ascites. RESULTS: During follow-up 74 (28.1%) patients developed DH, 30 (11.4%) RA (diuretic-resistant in 2 cases and diuretic-intractable because of the development of diuretic-induced complications in 28 cases), and 20 (7.6%) HRS (type 1, 7; type 2, 13). The 5-year probability of DH, RA, and HRS development was 37.1%, 11.4%, and 11.4%, respectively. The probability of survival at 1 and 5 years was 85% and 56.5%, respectively. The independent predictors for survival were baseline age, baseline Child-Pugh score, and DH development. The 1-year probability of survival after developing DH, RA, and type 2 HRS was 25.6%, 31.6%, and 38.5%, respectively. In contrast, the mean survival was only 7 +/- 2 days in those patients developing type 1 HRS. CONCLUSIONS: (1) The survival of cirrhotic patients with first episode of ascites is relatively high, and it is mainly influenced by age and Child-Pugh score at the time of ascites decompensation, as well as by DH development. (2) The probability of RA and HRS development is relatively low, but they are associated with a poor prognosis.

Probability of liver cancer and survival in HCV-related or alcoholic-decompensated cirrhosis. A study of 377 patients.

BACKGROUND: Although chronic alcohol intake and chronic hepatitis C may progress to cirrhosis and hepatocellular carcinoma (HCC), few data are available about survival and probability of developing HCC in decompensated cirrhosis of both aetiologies. METHODS: This study identified factors related with probability of developing HCC and survival in a cohort of 377 consecutive patients with decompensated HCV-related cirrhosis (200 cases) or alcoholic cirrhosis (177 cases) without known HCC, hospitalized for their first hepatic decompensation, as well as to evaluate differences between both aetiologies. Patients were followed for a mean period of 39 +/- 2 months. RESULTS: During follow-up, 42 patients (11.1%) developed HCC (16.5% vs 5.1%) in groups HCV and alcohol, respectively; p = 0.0008), and 131 patients (34.7%) died (42% vs 26.6% in groups HCV and alcohol, respectively; p = 0.002). Age and HCV-cirrhosis were independently related to HCC development, while baseline age and Child-Turcotte-Pugh score were independently correlated with survival. CONCLUSION: Survival in decompensated HCV-related or alcoholic cirrhosis is influenced by age and baseline Child-Turcotte-Pugh score, without differences in cirrhosis aetiology. The risk of developing HCC is greater in HCV-related cirrhosis than in alcoholic cirrhosis.

Natural history of decompensated hepatitis C virus-related cirrhosis. A study of 200 patients.

BACKGROUND/AIMS: Since few data are available concerning the clinical course of decompensated hepatitis C virus (HCV)-related cirrhosis, the aim of the present study was to define the natural long-term course after the first hepatic decompensation. METHODS: Cohort of 200 consecutive patients with HCV-related cirrhosis, and without known hepatocellular carcinoma (HCC), hospitalized for the first hepatic decompensation. RESULTS: Ascites was the most frequent first decompensation (48%), followed by portal hypertensive gastrointestinal bleeding (PHGB) (32.5%), severe bacterial infection (BI) (14.5%) and hepatic encephalopathy (HE) (5%). During follow-up (34+/-2 months) there were 519 readmissions, HCC developed in 33 (16.5%) patients, and death occurred in 85 patients (42.5%). The probability of survival after diagnosis of decompensated cirrhosis was 81.8 and 50.8% at 1 and 5 years, respectively. HE and/or ascites as the first hepatic decompensation, baseline Child-Pugh score, age, and presence of more than one decompensation during follow-up were independently correlated with survival. CONCLUSIONS: Once decompensated HCV-related cirrhosis was established, patients showed not only a very high frequency of readmissions, but also developed decompensations different from the initial one. These results contribute to defining the natural course and prognosis of decompensated HCV-related cirrhosis.