Search

Hemodialysis (HD) patients experience vascular calcification, ultimately leading to high mortality rates. Previously, we reported associations between soluble receptor for advanced glycation end products (sRAGEs) and extracellular newly identified RAGE-binding protein S100A12 (EN-RAGE) and vascular calcification. Here, we extended our observations, investigating whether these biomarkers may be useful for predicting cardiovascular morbidity and mortality in these subjects. Thus, we evaluated the relationship between sRAGE and S100A12 and mortality in long-term HD patients. This was a prospective observational cohort study in 199 HD patients from an extended analysis of our previous study. Plasma sRAGE, S100A12, comorbidities, and other traditional risk factors were investigated. The cumulative incidences for death using Cox proportional hazards regression were evaluated in multivariable analyses. The observation period was 44 months. During the observation period, 27 (13.6%) patients died. Univariate analysis demonstrated that S100A12 was correlated with diabetes (P = 0.040) and high-sensitivity C-reactive protein (hsCRP) (P = 0.006). In multivariable analyses, plasma sRAGE (hazard ratio [HR] = 1.155; 95% confidence interval [CI] = 0.612-2.183; P = 0.656) and S100A12 (HR = 0.960; 95% CI = 0.566-1.630; P = 0.881) were not associated with mortality in HD patients, although traditional predictors of mortality, including age, history of cardiovascular diseases (CVDs), and serum levels of albumin and hsCRP were related to mortality. Powerful predictors of mortality were age, CVD, and albumin levels. Plasma sRAGE and S100A12 may be weak surrogate markers for predicting all-cause mortality in patients undergoing HD, although S100A12 was partly related to diabetes and inflammation., Competing Interests: The authors have no potential conflicts of interest to disclose.

Metabolic acidosis, which is observed in salt-sensitive hypertension, is also associated with kidney injury. Alkali therapy in chronic renal failure (CRF) may ameliorate the progression of kidney disease; however, few studies have examined the effects of alkali therapy on salt sensitivity and kidney injury in CRF. We randomly administered standard diet (SD), sodium chloride with 20% casein diet (NACL), or sodium citrate with 20% casein diet (NACT) to Sprague-Dawley rats after a CRF or a sham operation. Four weeks after 5/6 nephrectomy, serum bicarbonate levels were higher in the NACT-treated group. On the pressure-natriuresis curve, NACT-treated CRF rats were more salt-resistant than NACL-treated CRF rats. Additionally, the NACT-treated CRF group showed less tubulointerstitial damage than the NACL-treated CRF group. The expression and immunoreactivity of NHE3 in the kidney in the NACT-treated CRF group were lower than those in the NACL-treated CRF group. We observed that dietary NACT as alkali therapy in CRF might improve the altered salt-sensitivity and ameliorate the progression of kidney injury compared to the NACL diet, which may be related to reduced renal NHE3 expression.

Malnutrition and inflammation are related to high rates of morbidity and mortality in hemodialysis patients. Resistin is associated with nutrition and inflammation. We attempted to determine whether resistin levels may predict clinical outcomes in hemodialysis patients. We conducted a prospective evaluation of 100 outpatients on hemodialysis in a single dialysis center (male, 46%; mean age, 53.7 ± 16.4 yr). We stratified the patients into 4 groups according to quartiles of serum resistin levels. During the 18-month observational period, patients with the lowest quartile of serum resistin levels had poor hospitalization-free survival (log rank test, P = 0.016). After adjustment of all co-variables, patients with the lowest quartile of serum resistin levels had poor hospitalization-free survival, compared with reference resistin levels. Higher levels of interleukin-6 were an independent predictor of poor hospitalization-free survival. In contrast, serum resistin levels were not correlated with interleukin-6 levels. The current data showed that low resistin levels may independently predict poor hospitalization free survival in hemodialysis patients.

The aim of this study was to assess immunohistochemical expression of p53, pRb, p16, and cyclin D1, alone or in combination, as prognostic indicators and to investigate their correlation with clinocopathologic features of urothelial carcinoma. Immunohistochemical staining for p53, pRb, p16, and cyclin D1 was performed on a tissue microarray from 103 patients with urothelial carcinoma who underwent radical cystectomy. Of the patient samples analyzed, 36 (35%), 61 (59%), 47 (46%) and 30 (29%) had altered expression of p53, pRb, p16, and cyclin D1, respectively. Abnormal expression of p53 and pRb correlated with depth of invasion (P=0.040 and P=0.044, respectively). Cyclin D1 expression was associated with tumor stage and recurrence (P=0.017 and P=0.036, respectively). Altered pRb was significantly correlated with overall survival (P=0.040). According to the expression pattern of pRb and p53, p53/pRb (altered/normal) had worse survival than p53/pRb (normal/altered) (P=0.022). Alteration of all markers had worse survival than all normal (P=0.029). As determined by multivariate analysis, tumor stage, lymph node metastasis and the combined expression of p53 and pRb are independent prognostic factors. In conclusion, immunohistochemical evaluation of cell cycle regulators, especially the p53/pRb combination, might be useful in planning appropriate treatment strategies.

Despite remarkable progress in understanding and treating gastrointestinal stromal tumors (GISTs) during the past two decades, the pathological characteristics of GISTs have not been made clear yet. Furthermore, concrete diagnostic criteria of malignant GISTs are still uncertain. We collected pathology reports of 1,227 GISTs from 38 hospitals in Korea between 2003 and 2004 and evaluated the efficacy of the NIH and AFIP classification schemes as well as the prognostic factors among pathologic findings. The incidence of GISTs in Korea is about 1.6 to 2.2 patients per 100,000. Extra-gastrointestinal GISTs (10.1%) are more common in Korea than in Western countries. In univariate analysis, gender, age, tumor location, size, mitosis, tumor necrosis, vascular and mucosal invasions, histologic type, CD34 and s-100 protein expression, and classifications by the NIH and AFIP criteria were found to be significantly correlated with patient's survival. However, the primary tumor location, stage and classification of the AFIP criteria were prognostically significant in predicting patient's survival in multivariate analysis. The GIST classification based on original tumor location, size, and mitosis is more efficient than the NIH criteria in predicting patient's survival, but the mechanism still needs to be clarified through future studies.

For intraoperative consultation of mucinous adenocarcinoma involving the ovary, it would be useful to have approaching methods in addition to the traditional limited microscopic findings in order to determine the nature of the tumors. Mucinous adenocarcinomas involving the ovaries were evaluated in 91 cases of metastatic mucinous adenocarcinomas and 19 cases of primary mucinous adenocarcinomas using both an original algorithm (unilateral >or=10 cm tumors were considered primary and unilateral <10 cm tumors or bilateral tumors were considered metastatic) and a modified cut-off size algorithm. With 10 cm, 13 cm, and 15 cm size cut-offs, the algorithm correctly classified primary and metastatic tumors in 82.7%, 87.3%, and 89.1% of cases and in 80.6%, 84.9%, and 87.1% of signet ring cell carcinoma (SRC) excluded cases. In total cases and SRC excluded cases, 98.0% and 97.2% of bilateral tumors were metastatic and 100% and 100% of unilateral tumors <10 cm were metastatic, respectively. In total cases and SRC excluded cases, 68.4% and 68.4% of unilateral tumors >or=15 cm were primary, respectively. The diagnostic algorithm using size and laterality, in addition to clinical history, preoperative image findings, and operative findings, is a useful adjunct tool for differentiation of metastatic mucinous adenocarcinomas from primary mucinous adenocarcinomas of the ovary.

The purpose of this prospective study was to verify and compare the strengths of various blood markers and fibrosis models in predicting significant liver fibrosis. One hundred fifty-eight patients with chronic liver disease who underwent liver biopsy were enrolled. The mean age was 41 yr and male patients accounted for 70.2%. The common causes of liver disease were hepatitis B (67.7%) and C (16.5%) and fatty liver (9.5%). Stages of liver fibrosis (F0-4) were assessed according to the Batts and Ludwig scoring system. Significant fibrosis was defined as > or =F2. Sixteen blood markers were measured along with liver biopsy, and estimates of hepatic fibrosis were calculated using various predictive models. Predictive accuracy was evaluated with a receiver-operating characteristics (ROC) curve. Liver biopsy revealed significant fibrosis in 106 cases (67.1%). On multivariate analysis, alpha2-macroglobulin, hyaluronic acid, and haptoglobin were found to be independently related to significant hepatic fibrosis. A new predictive model was constructed based on these variables, and its area under the ROC curve was 0.91 (95% confidence interval, 0.85-0.96). In conclusion, alpha2-macroglobulin, hyaluronic acid, and haptoglobin levels are independent predictors for significant hepatic fibrosis in chronic liver disease.

Thromboembolic events are reported to occur with a high frequency in the setting of malignancy. However, reports on an association between cholangiocarcinoma and pulmonary thromboembolism, thus far, are almost lacking. We present here an unusual case of a 56-yr-old patient presenting cholangiocarcinoma and unexplained pulmonary thromboembolism. The patient had been quite healthy before the diagnosis. Coagulation tests showed elevated levels of fibrinogen, fibrinogen degradation product (FDP), D-dimer, and IgM anticardiolipin antibody (aCL Ab). The thromboemboli were resolved 3 weeks after anticoagulant therapy using low molecular-weight-heparin. Then, follow-up coagulation tests showed a marked decrease to normal in aCL Ab titer as well as the normalization of FDP and D-dimer levels. In this case, we describe pulmonary thromboembolism caused by hypercoagulable state associated with cholangiocarcinoma and speculate that such a thrombotic phenomenon could be regressed by anticoagulant therapy.

Tumors of neuroepithelial origin are extremely rare in teratoma and tend to be derived from glial or primitive neuroectodermal cells. We describe a case of 2- month-old baby girl with an oligodendroglioma arising in an immature teratoma of the sacrococcygeal region. Histologically, the tumor was identical in appearance to low grade oligodendroglioma within the adult brain. Because immature teratoma was grade II, the patient received adjuvant chemotherapy. The patient died of progression of the intra-abdominal tumor 6 months after surgical excision. The authors believe this to be the first presentation in the world literature.

We report a case of renin-secreting juxtaglomerular cell tumor which developed in a hypertensive 47-yr-old Korean man. Presumptive clinical diagnosis was made before surgery based on the high level of plasma renin and the radiologic evidence of renal mass. Grossly, a round, bulging, well-encapsulated mass of 3 x 3 cm was located in the mid-portion of the right kidney. On microscopic examination, the tumor was composed of ovoid to polyhedral cells with bland nuclei, indistinct nucleoli and light eosinophilic cytoplasm. The immunostaining for renin showed strong positivity in the cytoplasm of tumor cells. The characteristic rhomboid shaped renin protogranules were observed in ultrastructural analysis.