CEA and CA19.9 as early predictors of progression in advanced/metastatic colorectal cancer patients receiving oxaliplatin-based chemotherapy and bevacizumab

We evaluated the changes of the tumor markers CEA and CA19.9 as early predictors of progression in metastatic colorectal cancer (mCRC) patients participating in a clinical study and receiving chemotherapy and bevacizumab (Bev). Seventy-two patients had high baseline CEA or CA19.9 serum levels. By ROC analyses, the areas under the curves were 0.83 for variable CEA cutoff values for distinguishing progressive disease (PD) versus stable disease (SD)/partial remission (PR)/complete remission (CR), and 0.80 for variable CA19.9 cutoff values for distinguishing PD versus SD/PR/CR. Rises in CEA and CA19.9 may early signal the occurrence of progression in mCRC patients receiving chemotherapy and Bev.     

A yeast-based genomic strategy highlights the cell protein networks altered by FTase inhibitor peptidomimetics

Background  

Farnesyltransferase inhibitors (FTIs) are anticancer agents developed to inhibit Ras oncoprotein activities. FTIs of different chemical structure act via a conserved mechanism in eukaryotic cells. They have low toxicity and are active on a wide range of tumors in cellular and animal models, independently of the Ras activation state. Their ultimate mechanism of action, however, remains undetermined. FTase has hundred of substrates in human cells, many of which play a pivotal role in either tumorigenesis or in pro-survival pathways. This lack of knowledge probably accounts for the failure of FTIs at clinical stage III for most of the malignancies treated, with the notable exception of haematological malignancies. Understanding which cellular pathways are the ultimate targets of FTIs in different tumor types and the basis of FTI resistance is required to improve the efficacy of FTIs in cancer treatment.     

The Italian Research Group for Gastric Cancer (GIRCG) guidelines for gastric cancer staging and treatment: 2015

Methodology for the diagnosis and staging of early gastric cancer (EGC) has improved in Japan since the development of the gastro-camera and determination of a definition of EGC. Imaging technology has been steadily evolving in the endoscopy field. Improvements in the resolution of standard endoscopy images used in screening and surveillance provide greater opportunities to find gastric cancer earlier. Image enhancement endoscopy (IEE), such as narrow band imaging (NBI), highlights mucosal structures and vascularity. In particular, when NBI is used with magnifying endoscopy, it reveals fine details of subtle superficial abnormalities of EGC that are difficult to recognize using standard white light endoscopy. IEE-assisted magnifying endoscopy has improved the accuracy of the differentiation of superficial gastric cancer as well as delineation of the diseased mucosa. The advanced imaging technology enables precise assessment of the risk of lymph node metastasis of EGC and is widely used to determine indications for endoscopic treatment. It is not an overstatement to say that this has become the basis for the current development and dissemination of endoscopic treatments. Moreover, the resolution of endoscopic imaging has been upgraded to the microscopy level by the development of endomicroscopy, including endocytoscopy and confocal laser endomicroscopy. Endomicroscopy allows real-time histological analysis of living tissue during routine endoscopy and may reduce the number of biopsies needed to reach the correct diagnosis, minimizing the risk of sampling errors.     

Proposal of a new stage grouping of gastric cancer for TNM classification: International Gastric Cancer Association staging project

Background

The current AJCC staging system for gastric cancer (AJCC7) incorporated several major revisions to the previous edition. The T and N categories and the stage groups were newly defined, and adenocarcinoma of the esophagogastric junction (EGJ) was reclassified and staged according to the esophageal system. Studies to validate these changes showed inconsistent results. The International Gastric Cancer Association (IGCA) launched a project to support evidence-based revisions to the next edition of the AJCC staging system.

Methods

Clinical and pathological data on patients who underwent curative gastrectomy at 59 institutions in 15 countries between 2000 and 2004 were retrospectively collected. Patients lost to follow-up within 5 years of surgery were excluded. Patients treated with neoadjuvant therapy were excluded. The data were analyzed in total, and separately by region of treatment.

Results

Of 25,411 eligible cases, 84.8 % were submitted from 24 institutions of Japan and Korea, 6.4 % from other Asian countries, and 8.8 % from 29 Western institutions. The T and N categories of AJCC7 clearly stratified the patient survival. Patients with pN3a and pN3b showed distinct prognosis in all regions, and by introducing pN3a and pN3b into a cluster analysis, we established a new stage grouping with better stratification than AJCC7, especially among stage III subgroups. Survival of Siewert type 2 and 3 EGJ tumors was better stratified by this IGCA stage grouping than by either esophageal or gastric scheme of AJCC7.

Conclusions

For the next revision of AJCC classification, we propose a new stage grouping based on a large, worldwide data collection.

     

Detection of Apoptosis in Peripheral Blood Cells of 31 Subjects Affected by Down Syndrome Before and After Zinc Therapy

Thirty-one patients affected by Down syndrome (DS) were investigated to study the presence of apoptosis in peripheral blood cells in relation to the plasma levels of zinc. Twelve patients had undergone therapy with ZnSO₄, while the remaining 19 were untreated. The presence of programmed cell death was evaluated by means of electron microscopy, in situ nick translation (NT), and agarose gel electrophoresis of DNA. These approaches evidenced the presence of apoptosis in peripheral blood cells of patients before therapy with ZnSO₄, while after zinc supplementation there was a reduction in the number of apoptotic cells. These results suggest that the process of programmed cell death in peripheral blood cells of patients with Down syndrome is related to the plasma levels of zinc ion.     

Evaluation of B-cell secretion and peripheral insulin resistance during pregnancy and after delivery in gestational diabetes mellitus with obesity

Summary Nine pregnant women with gestational diabetes mellitus (GDM) were studied. Six normal pregnant women and six normal nonpregnant women were evaluated as control groups. All the women underwent oral glucose tolerance test and glucose clamp during the third trimester of pregnancy and two months after delivery. During OGTT, glucose, C-peptide and insulin plasma levels were determined. C-peptide and insulin values in the late phase of OGTT were higher during pregancy than after delivery in both groups. In gestational diabetic women, the M-value in the second steady-state during glucose clamp was lower than in controls, both during pregnancy and after delivery. Nevertheless, in both groups the M-value during pregnancy was lower than after delivery. Moreover, in gestational diabetic women there was an inverse correlation between M-value in the second steady-state and ponderal excess index after delivery. In conclusion, the impaired peripheral glucose utilization and the pancreatic pattern of gestational diabetic women compared to normals suggested altered B-cell secretion response, increased peripheral resistance and overweight to be the main changes in GDM.     

Congenital hip dislocation. The clinico-echographic correlations

The authors report their experience with US of the hip in 200 children aged 9 days to 8 months. All the children previously were under-gone physical examination. The sonographic study was carried out with Graf's method. The clinical-sonographic correlation proves the utility of US as a screening method able to show early morphological and functional alterations in the hip. US is thus suggested as a valid alternative to conventional methods to use in those cases where either plastering or surgery is required.