A case of extensive bone marrow infiltration due to gastric cancer is reported. A 65-year old man with an acute episode of anemia (Hb 4.1 mg/dl) and dyspnea was admitted to the Medical Department of a general hospital. Bone marrow biopsy showed extensive paratrabecular infiltration of a poorly differentiated adenocarcinoma of gastric origin. The primary tumor in the stomach was confirmed, and the patient was referred to our Institute and treated with combination chemotherapy (FAMTX) for 6 cycles. Due to the disappearance of bone marrow infiltration, the patient was considered for curative resection of the primary gastric cancer. After 27 months the patient is alive and in clinical complete remission.

Gastric cancer with bone marrow invasion at presentation: case-report and review of the literature.

Hepatocellular carcinoma (HCC) accounts for most cases of liver cancer worldwide; contraction of hepatitis C (HCV) is considered a major risk factor for liver cancer even when individuals have not developed formal cirrhosis. Global, untargeted metabolic profiling methods were applied to serum samples from patients with either HCV alone or HCC (with underlying HCV). The main objective of the study was to identify metabolite based biomarkers associated with cancer risk, with the long term goal of ultimately improving early detection and prognosis. Serum global metabolite profiles from patients with HCC (n=37) and HCV (n=21) were obtained using high performance liquid chromatography-mass spectrometry (HPLC-MS) methods. The selection of statistically significant metabolites for partial least-squares discriminant analysis (PLS-DA) model creation based on biological and statistical significance was contrasted to that of a traditional approach utilizing p-values alone. A PLS-DA model created using the former approach resulted in a model with 92% sensitivity, 95% specificity, and an AUROC of 0.93. A series of PLS-DA models iteratively utilizing three to seven metabolites that were altered significantly (p<0.05) and sufficiently (FC≤0.7 or FC≥1.3) showed good performance using p-values alone; the best of these PLS-DA models was capable of generating 73% sensitivity, 95% specificity, and an AUROC of 0.92. Metabolic profiles derived from LC-MS readily distinguish patients with HCC and HCV from those with HCV only. Differences in the metabolic profiles between high-risk individuals and HCC indicate the possibility of identifying the early development of liver cancer in at risk patients. The use of biological significance as a selection process prior to PLS-DA modeling may offer improved probabilities for translation of newly discovered biomarkers to clinical application.

Detection of Hepatocellular Carcinoma in Hepatitis C Patients: Biomarker Discovery by LC-MS

Hepatic cirrhosis is a major health problem across the world, causing high morbidity and mortality. This disease has many etiologies, yet the result of chronic hepatic injury is hepatic fibrosis causing cirrhosis and hepatocellular carcinoma, as the liver’s architecture is progressively destroyed. While liver biopsy is currently the gold standard for fibrosis staging, it has significant disadvantages, leading to a growing interest in non-invasive markers. Direct biomarkers – hyaluronic acid, laminin, collagen type III N-peptide, type IV collagen and cholylglycine – are new and rarely applied in routine clinical practice. This is the case primarily because there is no general consensus regarding the clinical application and effectiveness of the individual biomarkers. The usage of these markers in routine clinical practice could be advantageous for patients with liver fibrosis, requiring a simple blood test instead of a biopsy. The former option would be especially attractive for patients who are contraindicated for the latter. This review summarizes recent findings on direct biomarkers of liver fibrosis and highlights their possible applications and potential benefit for liver fibrosis diagnostics and/or staging. 

/pdf/clinical-importance-of-laboratory-biomarkers-in-liver-1k7d7916.pdf

Clinical importance of laboratory biomarkers in liver fibrosis

Cholylglycine (CG) is an extremely important biomarker used to diagnose liver abnormalities. Herein, we report a novel nickel nanoparticle (NiNP)-assisted liquid crystal (LC) cell system that can be used to visualize the enzymatic activities between cholylglycine hydrolase (CGH) and CG. When doped with trace amounts of NiNPs, the nematic LC, 4-cyano-4′-pentylbiphenyl (5CB), exhibited a uniform homeotropic alignment that provided dark optical outputs under a polarizing optical microscope (POM), at the designed LC sensing cells. These cells were sandwiched between a pretreated gold surface and an indium tin oxide (ITO) glass surface. In this system, the LC molecules were disordered, producing bright optical signals when CG was introduced to the binding CGH immobilized gold surface. We determined the CG detection limit in the “10 pM” level, and quantitatively defined a working range of 0.1 nM to 1 μM. The mechanism of the topographical changes on the reacted surface that led to these results was also verified by atomic force microscopy (AFM). This innovative technique, with its simplified path, shows great advances when compared to existing commercially available enzymatic-based bioassays, and offers an easy-to-use principal allowing the fabrication of practical LC-based sensors for CG detection.

Visualization of cholylglycine hydrolase activities through nickel nanoparticle-assisted liquid crystal cells

Determining cholylglycine (CG) levels is of great importance in the detection of liver abnormalities. In this study, we present a novel liquid–crystal (LC)-based method assisted with cholylglycine hydrolase (CGH) for the optical detection of CG levels. The detection method is based on the disruption of the orientations of a nematic LC, 4-cyano-4′-pentylbiphenyl (5CB), doped with dodecyl aldehyde. Aldehyde-doped 5CB droplets were placed on pre-treated glass slides and patterned with solutions of interest. When in contact with a small drop of a CG aqueous solution, bright fan-shaped LC droplet patterns were observed under polarizing optical microscopy, indicating a planar orientation of LC at the aqueous/LC interface. However, aldehyde with short-alkyl chain couples with glycine released from the enzymatic reaction between CG and CGH forming amphiphilic Schiff bases, which display dark cross patterns of LC, suggesting a homeotropic orientation of the LC. This system may offer a highly sensitive and methodologically simple approach to determine CG levels for clinical diagnostics and commercial applications.

Optical imaging of cholylglycine by using liquid crystal droplet patterns on solid surfaces

In order to study the clinical significance of cholylglycine (CG), CG in both fasting levels and after oral loading of 300 mg ursodeoxycholic acid (UDCA) were determined by radioimmunoassay in 313 patients with various liver diseases. Elevated fasting CG levels were found in 66.6% of patients with acute hepatitis (AH), 34.8% chronic inactive hepatitis (CIH), 79.3% chronic active hepatitis (CAH), 97.1% liver cirrhosis (LC), 94.7% hepatocellular carcinoma (HCC), and 80% of gall stones (GS). Changes of fasting CG during the course of AH were found to be parallel with values of transaminases. On oral loading of UDCA, different CG responses were found in CIH and CAH, and in compensated and decompensated LC. From these results we concluded that the determinations of serum CG gave additional informations of various liver diseases.

Clinical usefulness of serum cholylglycine determination in various liver diseases.

A 44-year-old man with Borrmann type III gastric carcinoma initially presenting bone metastasis and later transverse myelopathy is reported. Chest and skull roentgenograms showed multiple punched-out lesions. A bone scintigram showed multiple abnormal uptake. Histological examinations of biopsy and autopsy materials revealed signet-ring cell carcinoma of the stomach. Disseminated carcinomatosis of the bone marrow was ruled out histologically and neither microangiopathic hemolytic anemia nor disseminated intravascular coagulopathy was observed. Because this patient with bone metastasis did not have metastasis to the liver and lungs we propose that a nonportal route through the vertebral venous plexus might be an alternative to the portal route of bone metastasis from gastric carcinoma. During the last 20 years, only 10 such cases including this one have been reported in Japan. Their prognosis was quite poor and in most of them the malignancy was either undifferentiated adenocarcinoma or signet-ring cell carcinoma. If a bone metastasis is found as the initial sign, physicians should keep in mind that the primary lesion might be in the stomach, or in the thyroid, kidney, lung or prostate as another point of search.

An unusual case of gastric carcinoma initially presenting bone metastasis and later transverse myelopathy.

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Clinical usefulness of serum cholylglycine determination in various liver diseases.

An unusual case of gastric carcinoma initially presenting bone metastasis and later transverse myelopathy.