Hepatic Stellate Cells May Relate to Progression of Intrahepatic Cholangiocarcinoma

Background  Although cumulative evidence supports the fact that stromal myofibroblasts promote tumor progression, the influence of myofibroblasts on intrahepatic cholangiocarcinoma (ICC) is unclear. We hypothesized that hepatic stellate (HS) cells can differentiate into myofibroblasts in ICC stroma and that they promote cancer progression. This study aims to: (1) assess the influence of myofibroblasts on the prognosis of ICC, (2) identify HS cells in ICC stroma, and (3) investigate the interaction between HS cells (LI90 and LX-2) and ICC cells (HuCCT-1 and MEC) in vitro. Methods  The association between α-smooth muscle actin (α-SMA) expression and the prognoses of 46 ICC patients after hepatic resection was evaluated by immunohistochemical analysis. The HS cells in myofibroblasts of ICC were identified (double immunostaining) using antibodies for α-SMA, glial fibrillary acidic protein (GFAP), and desmin. The influence of HS cells on the invasion and growth of ICC cells was examined in vitro using a coculture system. Results  Patients with high α-SMA expression exhibited the worse outcomes. Multivariate analyses revealed that high α-SMA expression (P = 0.0045) and positivity for lymph-node metastasis were independent prognostic factors. Because desmin- or GFAP-positive cells coexpressing α-SMA were observed in the ICC samples, they were considered to be derived from the HS cells. On coculturing with HS cells, a remarkable increase was observed in the invasion and growth of the two ICC cell lines. Conclusions  Stromal myofibroblasts may relate to the poor prognoses in ICC patients. HS cells appear to be involved in the progression of ICC.     

The impact of molecular profile on the lymphatic spread pattern in stage III colon cancer

The anatomical spread of lymph node (LN) metastasis is of practical importance in the surgical management of colon cancer (CC). We examined the effect of KRAS, BRAF, and microsatellite instability (MSI) on LN count and anatomical spread pattern in stage III CC. We determined KRAS, BRAF, and MSI status from stage III CC patients. Biomarker status was correlated with LN count and anatomical spread pattern, which was classified as sequential or skipped. Relapse-free survival (RFS) was estimated using Kaplan-Meier method, and correlations were assessed using log-rank and Cox regression analyses. We analyzed 369 stage III CC patients. The proportion of KRAS mutant (mt), BRAF mt, and MSI-high (H) were 44.2% (163/344), 6.8% (25/344), and 6.8% (25/344), respectively. The mean number of metastatic LN was higher in microsatellite-stable (MSS) compared with MSI patients (3.5 vs. 2.7, P = .0406), although no differences were observed in accordance with KRAS or BRAF status. Interestingly, patients with BRAF mt and MSI-H were less likely to harbor skipped metastatic LN (9.3% vs 20% and 4% vs 10.5% compared with BRAF wild-type (wt) and MSS, respectively), but KRAS status did not predict anatomical spread pattern. Patients with KRAS wt and MSI-H showed superior RFS compared with KRAS mt and MSS patients, respectively, whereas BRAF status did not affect RFS. Differences exist in the anatomical pattern of invaded LN in accordance with the molecular status of stage III CC. Patients with MSI-H CC have less invaded and skipped LN, suggesting that a tailored surgical approach is possible.     

Dietary palatinose and oleic acid ameliorate disorders of glucose and lipid metabolism in Zucker fatty rats

Excessive dietary intake of carbohydrates and fats has been linked to the development of obesity. However, the mechanism by which these dietary factors interact to bring about metabolic changes has not been elucidated. We examined the combined effects of different types of dietary carbohydrates and fats on the etiology of obesity and its complications in the Zucker fatty (fa/fa) rat, a model of obesity. Specifically, these rats were fed an isocaloric diet containing various combinations of carbohydrates [palatinose (P), an insulin-sparing sucrose analogue, and sucrose (S)] and fatty acids [oleic acid (O) and linoleic acid (L)]. After 8 wk, palatinose feeding (PO and PL) led to significant reductions in visceral fat mass, adipocyte cell size, hyperglycemia, and hyperlipidemia compared with sucrose feeding (SO and SL); pancreatic islet hypertrophy was also prevented by palatinose feeding. Linoleic-acid-fed rats (PL and SL) exhibited reduced insulin-immunoreactive staining of the pancreatic islets, enhanced macrophage infiltration in adipose tissue, and an elevated plasma tumor necrosis factor-alpha concentration when compared with oleic-acid-fed rats (PO and SO). Furthermore, sucrose and linoleic acid synergistically increased the expression of genes involved in hepatic gluconeogenesis and lipogenesis [sterol regulatory-element binding protein (SREBP)-1c and SREBP-2]. In conclusion, a diet containing palatinose and oleic acid may prevent diet-induced metabolic abnormalities. The combination of palatinose and oleic acid holds promise for a new approach to preventing and treating obesity and its complications.     

Relationship between cytokine concentration and activities of daily living in rehabilitation patients with stroke

Stroke rehabilitation is effective in some patients, however not so effective in others. Our ultimate aim is to use the clinical laboratory assessment as a tool for effectiveness discrimination in rehabilitation. Subjects were 15 stroke patients (68.1 +/- 12.7 years old) who were admitted to our convalescent rehabilitation wards. Fasting blood samples were analyzed for serum concentrations of hepatocyte growth factor (HGF), vascular endothelial growth factor (VEGF) and insulin-like growth factor-I (IGF-I) which are considered to be involved in hypermyotrophy using ELISA methods on admission and at discharge. Sixteen healthy control subjects (63.0 +/- 7.6 years old) were also employed. As accuracy control of these analyses, decrease of serum HGF after keeping at -20 degrees C for 499 days were measured. The concentration was 0.66ng/mL from 0.71 ng/mL and residual ratio was 94.0%. Reaction specificity to MW 60 kDa HGF antibody using the Western blot method was confirmed. Average HGF and VEGF were higher in stroke patients than those in control subjects. Average IGF-I was lower in stroke patients. The correlations between HGF, VEGF, and IGF-I and the score of activities of daily living expressed by the Functional Independence Measure (FIM) were calculated. Highest correlation coefficient of 0.67 (p < 0.01) was obtained between HGF at discharge and the FIM efficiency (the gain of the FIM during hospitalization divided by length of stay). The correlation coefficients related to VEGF or IGF showed lower value. High FIM efficiency denotes rapid recovery with vigorous exercise. HGF at discharge would reflect the result of high activity.     

The Impact of Histologic Liver Inflammation on Oncology and the Prognosis of Patients Undergoing Hepatectomy for Hepatocellular Carcinoma

Annals of Surgical Oncology - Liver inflammation is a reaction to disease-causing stress in the liver that induces fibrosis and cirrhosis. However, its prognostic impact after hepatectomy remains...     

Visualization of the heterogeneous internal structure of so-called "pancreatic necrosis" by magnetic resonance imaging in acute necrotizing pancreatitis

INTRODUCTION: Contrast-enhanced computed tomography (CT) is the gold standard for assessing the severity of acute pancreatitis, especially for evaluating the presence of pancreatic necrosis (poorly perfused area). However, the contrast medium used for CT is potentially toxic to the pancreas and kidney. Therefore, medical institutions without facilities for hemodialysis hesitate to acquire contrast-enhanced CT images. Diagnostic values of magnetic resonance imaging (MRI) in pancreatic diseases have been shown. AIM: To evaluate the usefulness of MRI in the assessment of the severity of acute pancreatitis. RESULTS: All necrotic regions in the pancreas were visualized by gadolinium-enhanced MRI. Furthermore, MRI can discriminate the poorly perfused pancreatic area, namely so-called "pancreatic necrosis" judged on CT, into three parts: 1) necrotic area of the pancreatic parenchyma, 2) perinecrotic fluid collection, and 3) hemorrhagic foci. Inflammatory changes that were required for severity grading were also evaluated sufficiently by MRI. CONCLUSION: These results suggest that MRI is useful for the assessment of severity of acute pancreatitis.     

Visualization of isolated conus artery as a major collateral pathway in patients with total left anterior descending artery occlusion

To examine the existence of isolated conus artery (ICA) as a source of collateral circulation, we selectively visualized the ICA in patients with left anterior descending coronary artery (LAD) occlusion using a no. 5 French catheter. One hundred and fifty patients with a total LAD occlusion were selected from 639 consecutive patients who had diagnostic coronary angiography during an 18-month period; the ICA was found in 45 patients. Among these patients, 30 showed the ICA as a collateral vessel supplying the distal LAD. In nine of these patients, conventional left and right coronary angiography did not reveal any other significant collateral vessels, and the distal LAD was perfused mainly by the collaterals from the ICA. No serious complications such as ventricular fibrillation or myocardial infarction occurred during these procedures. These results indicate that the selective ICA visualization is clinically important when conventional left and right angiography does not demonstrate collaterals to the obstructed LAD.     

Intracardiac flow pattern in mitral regurgitation studied with combined use of the ultrasonic pulsed doppler technique and cross-sectional echocardiography

Thirty patients with mitral regurgitation confirmed by left ventriculography were studied from a transcutaneous approach with combined use of the ultrasonic pulsed Doppler technique and cross-sectional echocardiography. The location of the abnormal Doppler signals was revealed with cross-sectional echocardiography, displayed in two dimensional images.Abnormal Doppler signals, never detected in healthy subjects, were recorded during systole at the mitral area and in the left atrial cavity in patients with mitral regurgitation.In the left atrial cavity, these signals were detected in 11 patients. They were either bidirectional or unidirectional and of a wide velocity range. The area in which these signals were detected was mapped on the cross-sectional echocardiogram, and the map was considered to show the main direction and distribution of regurgitant flow from the mitral ostium into the left atrial cavity. The main direction of the regurgitant flow determined with this method closely coincided with that revealed by angiocardiography.At the mitral area, abnormal Doppler signals were detected in 28 patients. These signals were powerful, bidirectional and of a wide range of velocity. It is believed that these signals indicate not only the mitral regurgitant flow, but also the vibration of the mitral valve. Thus, the combined use of the ultrasonic pulsed Doppler technique and cross-sectional echocardiography is advantageous for the transcutaneous detection and analysis of regurgitant flow in mitral regurgitation.     

Intrahepatic dissemination of hepatocellular carcinoma after local ablation therapy

Background/Purpose

We aimed to clarify the histological features of and risk factors for intrahepatic dissemination after local ablation therapy (LAT) for hepatocellular carcinoma (HCC).

Methods

Between April 1992 and December 2005, 192 HCC patients underwent hepatic resection at our department, among whom were 17 patients who had local recurrences after LAT. Eight of these 17 patients had intrahepatic dissemination. The clinical and histological characteristics of these 8 surgically treated patients with intrahepatic dissemination were investigated.

Results

Histologically, numerous intrahepatic metastases were observed, mainly in the same section as the treated tumor, together with main or sectional portal vein tumor thrombi. Before the ablation therapy, the average tumor diameter was 2.1 cm, and 62.5% of the tumors were adjacent to the main or sectional portal vein. In terms of therapeutic factors, 25% of the patients had a prior needle biopsy and 62.5% had insufficient safety margins.

Conclusions

LAT for HCCs (even those less than 3 cm in diameter) adjacent less than 5 mm to the main or sectional portal vein possibly promotes intrahepatic dissemination.