Elevated concentrations of γ-enolase in renal cell tumors in rats: similarity to renal cell carcinoma in man

Concentrations of enolase isozymes in normal kidney and renal cell tumors in rats were determined using a highly sensitive enzyme immunoassay, and the isozymes were immunohistochemically localized in tissue sections. Levels of -enolase in renal cell turnors were significantly lower than in normal kidney, whereas those of -enolase were significantly elevated (mean ±SD:211±129 ng/mg protein, n=15, as compared to 27.1±2.9 ng/mg protein, n=7). The proportion of -enolase in the total enolases in the tumor tissues (1.6±0.5%) was significantly higher than in normal kidney (0.15±0.005). Immunohistochemistry revealed epithelial cells of all nephron segments to be positive for the -isozyme, whereas -enolase staining was strongly positive only in the loops of Henle, being faint in the distal tubules and absent in the proximal tubules. Both - and -enolases demonstrated positive immunostaining in all of the seven renal cell tumors studied. These findings indicate that an isozyme switch from - to -enolase occurs during rat kidney carcinogenesis, taking into account the derivation from proximal tubules, consistent with the findings for renal cell carcinomas in man.     

Priority of Lymph Node Dissection for Siewert Type II/III Adenocarcinoma of the Esophagogastric Junction

Objective

The purpose of this study was to clarify the priority of nodal dissection in Siewert types II and III adenocarcinoma of the esophagogastric junction (AEG).

Methods

The priority of nodal dissection was evaluated based on the therapeutic value index calculated by multiplying of the frequency of metastasis to each station and the 5-year survival rate of patients with metastasis to that station.

Results

A total of 176 patients (95 type II and 81 type III) were examined. Among the lymph nodes that had a metastatic incidence exceeding 10 %, the stations showing the first to fourth highest index were the paracardial and lesser curvature nodes (Nos. 1, 2, and 3) and the node at the root of the left gastric artery (No. 7) in the total cohort, as well as in each type. The next station was the lower thoracic paraesophageal lymph node (No. 110), followed by the nodes along the proximal splenic artery (No. 11p) in type II, whereas it was the nodes along the proximal splenic artery (No. 11p) followed by the para-aortic nodes (No. 16a2), the nodes at the celiac artery (No. 9), and the nodes around the splenic hilum (No. 10) in type III.

Conclusions

These results suggest that the highest priority nodal stations to be dissected were the paracardial and lesser curvature nodes (Nos. 1, 2, and 3) and the nodes at the root of the left gastric artery (No. 7), regardless of the Siewert subtype, but the subsequent priority was different depending on the subtype.     

Dual role of vascular endothelial growth factor in hepatic ischemia-reperfusion injury

BACKGROUND: Vascular endothelial growth factor (VEGF), a major angiogenic factor, mediates a variety of disease conditions through promotion of angiogenesis. It also plays a critical role as a potent proinflammatory cytokine in a variety of physiologic and pathologic immune responses. In the present study, we evaluated the expression of VEGF in hepatic warm ischemia-reperfusion (I/R) injury and examined the effect of recombinant human (rh)VEGF administration in an established murine model. METHOD: The expression of VEGF in the liver was assessed by quantitative real-time polymerase chain reaction and immunohistochemistry during I/R injury using 70% partial hepatic ischemia model. The effect of rhVEGF administration on I/R injury was evaluated by measuring liver function and histology. In addition, local inducible nitric oxide synthase (iNOS) and endothelial NO synthase expressions were examined to address the underlying mechanisms. RESULTS: The local expression of VEGF was significantly up-regulated at 2 hours after reperfusion after 60 minutes of ischemia compared with that in the naive liver. VEGF was expressed predominantly in CD11b+ cells infiltrating into the ischemic liver. The administration of rhVEGF had a significant protective effect on ischemic injury in the liver. This effect was associated with the up-regulation of iNOS expression in the rhVEGF-treated liver. CONCLUSION: We demonstrate a dual role of VEGF in hepatic warm I/R injury. Although endogenous VEGF is expressed and functional to initiate hepatic I/R injury, exogenous rhVEGF has a beneficial effect on the ischemic liver. These data may provide new insights into the role of VEGF as well as pathophysiology of hepatic I/R injury.     

Neurotoxicity induced by tacrolimus after liver transplantation: relation to genetic polymorphisms of the ABCB1 (MDR1) gene

BACKGROUND: Tacrolimus is a substrate of P-glycoprotein (PGP) encoded by the multidrug resistant (MDR)1 gene (ABCB1). PGP, a multidrug efflux pump, restricts the distribution of tacrolimus in the brain. In this study, we investigate the correlation of ABCB1 gene polymorphism with tacrolimus-induced neurotoxicity in patients after liver transplantation. METHODS: The genotype of 6 patients with neurotoxic events and 11 patients without neurotoxic events was analyzed by polymerase chain reaction (PCR), and 8 mutations were detected. In addition to laboratory findings and patient characteristics, the contribution of mutations in the ABCB1 gene was evaluated with stepwise discriminant function analysis. RESULTS: High tacrolimus concentration, liver dysfunction, and mutation at position 2677 in exon 21 were demonstrated as positive predictors of tacrolimus-induced neurotoxicity. CONCLUSION: It is indicated that blood concentrations, liver function, graft weight, and polymorphism in the ABCB1 gene are important factors in tacrolimus-induced neurotoxicity.     

Evaluation of the association between locomotive syndrome and metabolic syndrome

Background

Locomotive syndrome (LS) includes disorders of the musculoskeletal system and is a high-risk condition that requires nursing care. We included an examination of locomotive function in specific health checkups to investigate the relationship between LS risk and the muscle strengths. The purpose of this study was to determine the distribution of LS and the relationship between LS and metabolic syndrome (MetS).

Laparoscopic Versus Open Multivisceral Resection for Primary Colorectal Cancer: Comparison of Perioperative Outcomes

Background

The role of laparoscopic surgery for locally advanced colorectal cancer invading or adhering to neighboring organs is controversial. This study evaluated the safety and feasibility of laparoscopic multivisceral resection for colorectal cancer.

Methods

This study included 126 patients who underwent multivisceral resection for primary colorectal cancer invading or adhering to neighboring organs or structures between July 2005 and November 2012 at our institution. Perioperative outcomes were compared between laparoscopic and open resections.

Results

Laparoscopic and open multivisceral resections were performed in 60 and 66 patients, respectively. Conversion to open surgery occurred in 6.7 % of patients. The median operative time was significantly longer (271 vs. 227 min), but the median blood loss was significantly less (40 vs. 205 mL), in the laparoscopic compared with the open group. The R0 resection rate of the primary tumor (95 vs. 98.5 %), number of lymph nodes harvested (18 vs. 18), and postoperative complications (28 vs. 24 %) were comparable between the groups. The median length of hospital stay was significantly shorter (13.5 vs. 18 days) in the laparoscopic compared with the open group.

Conclusions

Laparoscopic multivisceral resection for colorectal cancer invading or adhering to neighboring organs is safe and feasible in selected patients.     

The Evaluation of Duct-to-mucosal Pancreaticojejunostomy in pancreaticoduodenectomy

This study was conducted to examine the efficacy of duct-to-mucosal pancreaticojejunostomy compared with external stented pancreaticojejunostomy in prevention of several complications, retrospectively. Seventy-six patients with pancreatic head resection (59 male; median age, 60.1 years) underwent pancreaticoduodenectomy at the Second Department of Surgery, Wakayama Medical University, School of Medicine, Wakayama, Japan, between January 1, 1994, and March 31, 2002. In early postoperative status, the incidence of pancreatic fistula by duct-to-mucosal anastomosis (n = 45) was similar to that by external stent (n = 31); soft pancreas is a risk factor of pancreatic fistula compared with hard pancreas (p < 0.05). During the late postoperative period, however, no patients with duct-to-mucosal anastomosis showed pancreatic duct dilatation by computed tomography (CT). At the same time, 58.8% of patients with external stent followed by CT showed pancreatic duct dilatation (p < 0.01). The duct-to-mucosal anastomosis was more effective pancreaticojejunostomy than the external stent in terms of prevention of pancreatic duct dilatation, and it should be the surgical procedure of choice in pancreaticoduodenectomy.     

Effects of cinacalcet on bone mineral density and bone markers in hemodialysis patients with secondary hyperparathyroidism

Background

Cinacalcet markedly reduces the serum intact parathyroid hormone (PTH) level of hemodialysis (HD) patients with secondary hyperparathyroidism. Parathyroidectomy also reduces the serum intact PTH level of HD patients and it increases their bone mineral density (BMD). However, there is little information about the effect of cinacalcet on BMD or on the associations between bone markers and BMD in HD patients.

Methods

We performed a 1-year cohort study of 25 HD patients who had a serum intact PTH level above 300 pg/ml during treatment by conventional therapies, such as with active vitamin D, and cinacalcet was prescribed for 14 of them. BMD of the femoral neck and the serum levels of two circulating bone markers, alkaline phosphatase (ALP) and bone-specific alkaline phosphatase (BSAP), were measured before and after treatment. The other 11 HD patients without cinacalcet treatment were defined as control group.

Results

BMD significantly increased by 7.3 % during the 1 year of treatment in the cinacalcet group and decreased by 6.2 % during the same period in the control group, and cinacalcet therapy was independently associated with the changes in BMD after multiple regression analysis that included intact PTH (β = 7.57, P < 0.01). In the cinacalcet group, the serum ALP levels (R ² = 0.315, P < 0.05) and BSAP levels (R ² = 0.682, P < 0.01) levels were significantly negatively correlated with the changes in BMD, but the serum intact PTH levels were not significantly associated with the changes in BMD (R ² = 0.011, P = 0.72).

Conclusions

One year of treatment with cinacalcet increased the BMD of the femoral neck in the HD cohort, especially in the patients who had higher serum ALP and BSAP levels at baseline.     

Maximum Preservation of the Media in Carotid Endarterectomy

Carotid endarterectomy (CEA) is intended to remove atheromatous plaque by dissecting a plane between the intima and the media (circular medial fibers), but this may not be the optimal dissection plane. The present technique is based on identifying the plane that divides the media from the plaque, so preserving the media on the adventitia as much as possible. This plane is more difficult to find and follow than the easy-to-dissect plane usually located between the media and the adventitia, because the plaque invades the media and so the dividing plane is located within the media. In this prospective observational study, CEA was performed in 22 patients to histologically examine the excised plaques and small samples of the whole arterial wall, and evaluate the clinical outcomes. Plaque had invaded the luminal part of the media in the whole arterial wall sample of 80% of cases. Thin medial layers covering > 80% of the surface of the plaque were found in 16 of 22 plaques (73%). Some atheromatous component was sometimes left in the preserved media, rather than completely removed with the media. No morbidity or mortality had occurred by discharge. Only 1 small ipsilateral infarction (4.5%) and no restenosis of greater than 50% were detected during the mean follow-up period of 7 years. Since the plaque usually invades the media, the optimum dissection plane may be located within the media, dividing it into two layers. The presence of some remnant atheromatous components in the preserved media was not associated with surgical complications or restenosis.     

Navigator-echo-based MR provides high-resolution images and precise volumetry of swine livers without breath holding or injection of contrast media.

The accurate calculation of hepatic volume by computed tomography (CT) or magnetic resonance (MR) is complicated by the need for breath holding and the injection of contrast media. These are often contraindicated in patients with liver failure, and we examined the ability of unenhanced 3-dimensional (3-D) navigator-echo-based MR (NE-MR) to accurately image livers and measure volumes without breath holding compared to unenhanced (plain) or gadolinium-diethylene triamine pentaacetic acid enhanced MR (Gd-MR) in miniature swine (n = 8). Without breath holding, diaphragm movement monitoring with NE-MR reduced motion artifacts in hepatic images compared with the other modalities. Without the injection of contrast media, the signal-to-noise ratios of the images obtained using NE-MR were significantly higher than those from plain MR; Gd-MR was superior to NE-MR, however (79.5 +/- 7.5 vs. 63.2 +/- 6.0 or 97.8 +/- 8.1, respectively; P < 0.01 for each). Overall, NE-MR produced improved high-resolution liver images. Consequently, liver volumes calculated based on NE-MR images were more highly correlated with actual liver weights compared to plain or Gd-MR in the whole livers (n = 8; r = 0.937 vs. 0.835 or 0.904, respectively). Also, NE-MR demonstrated significantly strong correlation between actual weights and volumetry-calculated volumes in regenerative livers 7 days after massive hepatectomy (n = 10, r = 0.989, P < 0.01). In conclusion, our results indicate that without breath holding or the injection of contrast media, 3-D NE-MR can provide both high-resolution liver images and precise hepatic volumes in patients with liver failure due to liver surgery (massive hepatectomy and living donor liver transplantation) or fulminant hepatic failure.