Clinical significance of vascular endothelial growth factor and hepatocyte growth factor in multiple myeloma

Angiogenesis is a crucial process in the progression of multiple myeloma (MM). Vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF) are multifunctional cytokines that potently stimulate angiogenesis including tumour neovascularization. Serum levels of VEGF and HGF were measured in 52 patients with MM by enzyme-linked immunosorbent assay (ELISA). Serum levels of VEGF and HGF were elevated in MM patients compared with healthy controls (VEGF: mean 0.31 ng/ml and 0.08 ng/ml respectively, P < 0.01; HGF: mean 2.17 ng/ml and 0.45 ng/ml, respectively, P < 0.001). In serial samples taken after chemotherapy, serum VEGF and HGF levels were correlated with M-protein levels. Serum levels of VEGF were higher in patients with extramedullary plasmacytomas than in patients without them (P < 0.05). They were also significantly higher in a group of patients who showed poor response to chemotherapy (P < 0.01). Serum levels of HGF were higher in patients with complications such as anaemia, hypercalcaemia and amyloidosis than in patients without these complications (P < 0.01, P < 0.05, P < 0.05 respectively). Both serum VEGF and HGF levels were significant predictors of mortality (P = 0.01, P = 0.02, respectively, log-rank test). The present study demonstrated that serum levels of VEGF and HGF are significantly elevated and dependent on the severity of MM, suggesting that measurement of VEGF and HGF may be useful for assessing disease progression and for predicting the response to chemotherapy in MM patients.     

Chronic pancreatitis at early age of onset presenting interesting findings through endoscopic retrograde pancreatography and chemical analysis of nonopaque pancreatic concretion

Summary This case concerns a 20-year-old male patient with an approximate 10-year history of recurrent and severe abdominal pain radiating to the back. Endoscopic retrograde cholangiopancreatography revealed a short obstructing stenosis of the main pancreatic duct in the head of the pancreas, marked and tortuous dilatation of the prestenotic portion of the main pancreatic duct and its side branches, and a filling defect in the side branch in the body of the gland. Pancreaticojejunostomy was performed to induce decompression of the pancreatic duct. Histology of the pancreas showed advanced chronic pancreatitis. Three nonopaque concretions were obtained at operation. The largest one, which was milky white in appearance and elastic and soft in consistency, proved to be made up of protein. The concretion was rich in acidic amino acids, but poor in basic or aromatic residues. The molar composition of amino acids in the concretion was, in decreasing order, aspartic acid, serine, valine, glycine, and glutamic acid. Powder x-ray diffractometry revealed no crystalline structures.     

Atheromatous plaque in the distal aortic arch creating the potential for cerebral embolism during cardiopulmonary bypass

The present study evaluated the risk in cardiac patients of rupture of a plaque by a jet stream from the arch cannula. The entire thoracic aorta and cardiac function were routinely monitored by transesophageal echocardiography (TEE) in 88 adult patients who underwent coronary artery bypass surgery. The changes in the atheromatous plaque in the distal aortic arch were observed before and after cardiopulmonary bypass. Of the 88 patients, 13 were found to have preoperative atheromatous plaque at the distal aortic arch and 8 (61.5%) of them suffered plaque rupture caused by jet stream from the arch cannula. Only 1 patient experienced apparent embolic episodes manifesting as cerebral and left leg embolisms; the remaining 7 had no clinical embolic symptoms. In order to prevent atheroembolic events, attention should be paid not only to the ascending aorta, but also to the distal arch and in this regard TEE is useful for detecting atheromatous changes of the aorta.     

FER overexpression is associated with poor postoperative prognosis and cancer-cell survival in non-small cell lung cancer

Here, we show that overexpression of fer tyrosine kinase (FER), a non-receptor tyrosine kinase, predicts poor postoperative outcome and might be involved in cancer-cell survival in non-small cell lung cancer (NSCLC). Systematic screening using in silico analyses and quantitative RT-PCR revealed that FER was overexpressed in about 10% of NSCLC patients. Evaluation of FER expression using immunohistochemistry (IHC) on tissue microarrays was consistent with the mRNA level detected using quantitative RT-PCR. In analyses of 135 NSCLC patients who had undergone potential curative resection, we found that FER overexpression detected using IHC had no association with clinicopathological features such as age, sex, smoking history, histological type, disease stage, T factor, N factor, adjuvant chemotherapy history, or EGFR mutation, but was correlated with poor postoperative survival periods. A multivariate Cox regression analysis showed that this prognostic impact was independent of other clinicopathological features. In functional analyses of FER in vitro, FER exhibited a transforming activity, suggesting that it possesses oncogenic functions. We also found that human lung cancer NCI-H661 cells, which exhibited FER-outlier expression, were led to apoptosis by the knockdown of FER using RNA interference. FER overexpression might serve as a prognostic biomarker and be involved in cancer-cell survival in NSCLC.