Postoperative development of sarcopenia is a strong predictor of a poor prognosis in patients with adenocarcinoma of the esophagogastric junction and upper gastric cancer

Background

There were few studies assessed the postoperative sarcopenia in patients with cancers. The objective of present study was to assess whether postoperative development of sarcopenia could predict a poor prognosis in patients with adenocarcinoma of esophagogastric junction, (AEG) and upper gastric cancer (UGC).

Association of kidney function with cancer incidence and its influence on cancer risk of smoking: The Japan Multi-Institutional Collaborative Cohort Study

The association between kidney function and cancer incidence is inconsistent among previous reports, and data on the Japanese population are lacking. It is unknown whether kidney function modifies the cancer risk of other factors. We aimed to evaluate the association of estimated glomerular filtration rate (eGFR) with cancer incidence and mortality in 55 242 participants (median age, 57 years; 55% women) from the Japan Multi-Institutional Collaborative Cohort Study. We also investigated differences in cancer risk factors between individuals with and without kidney dysfunction. During a median 9.3-year follow-up period, 4278 (7.7%) subjects developed cancer. Moderately low and high eGFRs were associated with higher cancer incidence; compared with eGFR of 60-74 ml/min/1.73 m², the adjusted hazard ratios (HRs) (95% confidence intervals [CIs]) for eGFRs of ≥90, 75-89, 45-59, 30-44 and 10-29 ml/min/1.73 m² were 1.18 (1.07-1.29), 1.09 (1.01-1.17), 0.93 (0.83-1.04), 1.36 (1.00-1.84) and 1.12 (0.55-2.26), respectively. High eGFR was associated with higher cancer mortality, while low eGFR was not; the adjusted subdistribution HRs (95% CIs) for eGFRs of ≥90 and 75-89 ml/min/1.73 m² were 1.58 (1.29-1.94) and 1.27 (1.08-1.50), respectively. Subgroup analyses of participants with eGFRs ≥60 and <60 ml/min/1.73 m² revealed elevated cancer risks of smoking and family history of cancer in those with eGFR <60 ml/min/1.73 m², with significant interactions. Our findings suggest that the relationship between eGFR and cancer incidence was U-shaped. Only high eGFR was associated with cancer mortality. Kidney dysfunction enhanced cancer risk from smoking.     

Vitamin D,Cardiovascular System,and Longevity of Hemodialysis Patients

Abstract: The risk of cardiovascular death is high in hemodialysis (HD) patients, and thickening, stiffening and calcification of the arterial wall have been shown as its predictive factors. Activated vitamin D preparations are used for the treatment of secondary hyperparathyroidism in HD patients, but as they increase serum phosphate and calcium concentrations, there is a concern that they promote vascular calcification and, consequently, exacerbate the outcomes. In this article, the effects of vitamin D therapy on survival, cardiac function, arteriosclerosis, immunity, and inflammation are evaluated by reviewing the literature. In HD patients, the risk of death (particularly cardiovascular death) is significantly lower in those treated than in those not treated with vitamin D. Moreover, activated vitamin D improves cardiac function and alleviates cardiac hypertrophy in HD patients. Experimental data in cultured macrophages, vascular smooth muscle cells, and vascular endothelial cells suggest that it has antiatherosclerotic effects. In vivo, the administration of vitamin D improves immune functions and normalizes inflammatory reactions. In HD patients, vascular calcification is related to the dose of calcium carbonate, but its relationship with the administration of vitamin D is not significant. These observations suggest that, contrary to the general concerns, activated vitamin D exerts favorable effects on the cardiovascular system in HD patients as long as it is used in appropriate clinical doses.     

Cibenzoline-induced respiratory muscular paralysis in a hemodialysis patient

A 69-year-old man was admitted to our kidney center with endstage renal failure. We started intermittent peritoneal dialysis immediately because of severe azotemia, hyperkalemia, and metabolic acidosis. Two weeks after admission, he developed uremic pericarditis with frequent ventricular premature contractions and supraventricular premature contractions. The intermittent peritoneal dialysis was then replaced by intensive hemodialysis, and oral administration of 300 mg/d of cibenzoline was started. Four days later, he developed thirst, weakness, and dyspnea due to respiratory muscular paralysis. We initiated respiratory support with a respirator because analysis of his blood gases revealed marked hypercapnia and hypoxia. He also developed hypoglycemia and prolonged PQ and QRS intervals on the electrocardiogram, which we believed were due to cibenzoline intoxication; we discontinued the cibenzoline immediately. All symptoms improved, and he was extubated 5 days later. After 2 months, his pericardial effusion disappeared. He now continues maintenance hemodialysis as an outpatient. We suspect that the cibenzoline induced the respiratory muscular paralysis for 2 reasons: 1) the patient experienced the respiratory muscular paralysis, at the same time he also experienced thirst, weakness, hypoglycemia, and prolonged PQ and QRS intervals on electrocardiogram, and all of these symptoms improved after the discontinuation of cibenzoline, and 2) his plasma concentration of cibenzoline became remarkably elevated, to 20 times above the standard therapeutic level. This patient's clinical course indicates that hemodialysis might be superior to intermittent peritoneal dialysis for treatment of cibenzoline intoxication.     

Plasma leptin level and its relationship with body composition in hemodialysis patients

Leptin is a newly found hormone secreted by adipocytes that regulates food intake, thermogenesis, and body fat. We measured plasma leptin levels in 103 patients with chronic renal failure treated by hemodialysis and 167 age- and gender-matched healthy control subjects to examine the impact of renal failure on plasma leptin levels and the influence of leptin on body composition measured by dual-energy X-ray absorptiometry. Hemodialysis patients showed a significant decrease in both body fat mass and lean body mass compared with those of the control subjects. Plasma leptin was significantly elevated in the hemodialysis group over the controls. In both groups, leptin was higher in female than male subjects, and it correlated positively with percent body fat. The subjects were divided into six categories according to percent body fat, and plasma leptin levels were compared between the two groups in the same category. Leptin of hemodialysis patients was significantly higher than that of the control subjects in the percent body fat categories of 30 or greater, whereas there was no statistically significant difference in leptin concentrations in the lower percent body fat categories. This was also true in the comparison in each gender, and leptin levels in female subjects showed a more remarkable difference between the hemodialysis and control groups in obese categories. Multiple regression analysis in all subjects indicated that plasma leptin levels were independently affected by percent body fat, plasma insulin concentration, gender, and renal failure. The positive impact of renal failure on leptin remained significant in the subjects with percent body fat of 30 or greater in the multiple regression model, whereas it was no longer significant in the remaining lean subjects. In multiple regression analysis of factors affecting fat mass index and lean mass index, leptin level was selectively associated with fat mass index, but not with lean mass index, regardless of percent body fat ranges. These results indicate that renal failure is an important factor affecting plasma leptin levels, especially in obese female subjects, and that hyperleptinemia was closely related to fat mass but not to lean body mass in hemodialysis patients.     

A case of cystadenocarcinoma of the liver

A case of cystadenocarcinoma of the liver is reported. The patient was a 73-year-old woman in whom a tumor was detected in the lateral segment of the liver during a health examination. Ultrasonograms and computed tomograms showed a multilocular cystic mass. Magnetic resonance imaging (MRI) showed a multilocular lowintensity mass, including a high-intensity portion and a portal branch compressed by the tumor. MRI with gadolinium showed an enhanced cyst wall. The cystic part of the tumor became smaller and the solid part became larger over a 1-month period, indicating that the tumor was malignant. Subsegmentectomy (S₃) was performed and cystadenocarcinoma with cystadenoma was diagnosed by histopathological examination. Identification of changes in the appearance of a tumor should be helpful for the differential diagnosis of cystadenoma and cystadenocarcinoma.     

A patient with lambda type light-chain disease associated with Crow-Fukase syndrome and autoimmune thrombocytopenia]

A 67-year-old woman, who presented polyneuropathy, pleural effusion, ascites and sclerosing changes in the ribs, was admitted to our hospital on June 17, 1987. On admission, cerebrospinal examination showed a marked protein-cell dissociation and a delay in nerve conduction velocity. Bence-Jones protein was detected in urine, and the immunohistochemical study of biopsied bone marrow of the rib revealed lambda-chain positive plasmacytoma. Serum immunoelectrophoresis, however, showed no monoclonal gamma-globulinemia. From the findings described above, she was diagnosed as having Crow-Fukase syndrome associated with lambda-type light chain disease. Even with a therapy by prednisolone, platelet counts progressively declined to 10,000/ml3. Bone marrow aspiration showed normal number of megakaryocytes. Since platelet-associated IgG was increased to 452 ng/1.0 x 10(8) plt, a diagnosis of autoimmune thrombocytopenia was considered. Melphalan and cyclophosphamide to plasmacytoma resulted in a marked improvement of platelets. In addition, the level of platelet-associated IgG returned to normal range. Polyneuropathy, however, didn't respond to those therapies. It was suggested that both Crow-Fukase syndrome and thrombocytopenia were closely concerned with plasmacytoma but developed in a different manner.     

Cancer detection using a PET tracer, 11C-glycylsarcosine, targeted to H+/peptide transporter.

H+/peptide transporter, PEPT1, is functionally expressed in some human cancer cell lines and might be a candidate molecular target for detection of cancers in vivo using PET. The aim of the present study was to establish a novel tumor-imaging technology using a PET tracer targeted to H+/peptide transporter(s). We also compared the tracer with 18F-FDG, focusing on the specificity of their accumulation between tumor and inflammatory tissues. METHODS: A dipeptide PET tracer, 11C-glycylsarcosine (11C-Gly-Sar), was injected intravenously into athymic mice transplanted with human pancreatic, prostate, and gastric cancer cells. The distribution patterns of 11C-Gly-Sar and 18F-FDG in the tumor-bearing mice, and in mice with inflammatory tissue, were assessed by imaging with a positron planar imaging system (PPIS). Tissue distributions of tracer radioactivity were also measured. The expression levels of PEPT1 and PEPT2 (PEPTs) proteins in tumor xenografts and inflammatory tissue were examined by immunohistochemical analysis. The messenger RNA expression levels of PEPTs in 58 available cancer cell lines were quantified by means of real-time polymerase chain reaction. RESULTS: All 3 tumor xenografts were well visualized with the PPIS after injection of 11C-Gly-Sar. Expression of PEPTs in those xenografts was confirmed by immunohistochemical analysis. Tumor-to-blood concentration ratios of 11C-Gly-Sar increased in a time-dependent manner and were much higher than unity. Most of the radioactivity found in the tumor tissue was recovered as the intact tracer. These results indicated that 11C-Gly-Sar was taken up by the PEPTs in tumor xenografts. It is noteworthy that 11C-Gly-Sar was minimally present in inflammatory tissues that expressed no PEPT1 or PEPT2 protein, whereas 18F-FDG was highly accumulated, with the values of the selectivity index being >25.1 and 0.72 for 11C-Gly-Sar and 18F-FDG, respectively. The mRNAs of PEPT1 and PEPT2 were expressed in 27.6% and 93.1%, respectively, of the cancer cell lines examined in the present study. CONCLUSION: The present study indicates that 11C-Gly-Sar is a promising tumor-imaging agent and is superior to 18F-FDG for distinguishing between tumors and inflammatory tissue. Because PEPTs were ubiquitously expressed in various types of tumor cells examined, 11C-Gly-Sar could be useful for the detection of many types of cancers.     

Big mitogen-activated protein kinase 1 (BMK1)/extracellular signal regulated kinase 5 (ERK5) is involved in platelet-derived growth factor (PDGF)-induced vascular smooth muscle cell migration

Big mitogen-activated protein kinase 1 (BMK1), also known as extracellular signal-regulated kinase 5 (ERK5), is a newly identified member of the mitogen-activated protein (MAP) kinase family. Recently, several studies have suggested that BMK1 plays an important role in the pathogenesis of cardiovascular disease. To clarify the pathophysiological significance of BMK1 in the process of vascular remodeling, we explored the molecular mechanisms of BMK1 activation in vascular smooth muscle cells (VSMCs). From the results of co-immunoprecipitation and immunoblotting analyses, it was found that platelet-derived growth factor (PDGF), a known potent mitogen, activated BMK1 and triggered the Gab1-SHP-2 interaction in rat aortic smooth muscle cells (RASMCs). The abrogation of SHP-2 phosphatase activity by transfection of the SHP-2-C/S mutant suppressed PDGF-stimulated BMK1 activation. Infection with an adenoviral vector expressing dominant-negative MEK5alpha, which can suppress PDGF-stimulated BMK1 activation to the control level, inhibited PDGF-induced RASMC migration. Moreover, we observed an increase of BMK1 activation in injured mouse femoral arteries. From these findings, it is suggested that BMK1 activation leads to VSMC migration induced by PDGF via Gab1-SHP-2 interaction, and that BMK1-mediated VSMC migration may play a role in the pathogenesis of vascular remodeling.