Noriyuki Miyama

Surgical Resection and Inferior Vena Cava Reconstruction for Treatment of the Malignant Tumor: Technical Success and Outcomes

OBJECTIVE The purpose of this study was to review patients who underwent inferior vena cava (IVC) resection with concomitant malignant tumor resection and to consider the operative procedures and the outcomes. MATERIALS AND METHODS Between 2000 and 2012, 41 patients underwent resection of malignant tumors concomitant with surgical resection of the IVC at our institute. The records of these patients were retrospectively reviewed. RESULTS Primary tumor resections included nephrectomy, hepatectomy, retroperitoneal tumor extirpation, lymph node dissection, and pancreaticoduodenectomy. The IVC interventions were partial resection in 23 patients and total resection in 18 patients. Four patients underwent IVC replacement. Operation-related complications included pulmonary embolism, acute myocardial infarction, deep vein thrombosis, leg edema and temporary hemodialysis. There were no operative deaths. The mean follow-up period was 24.9 months (range: 2-98 months). The prognosis depended on the type and stage of the tumor. CONCLUSION Resection and reconstruction of the IVC can be performed safely if the preoperative evaluations and surgical procedures are performed properly. The IVC resection without reconstruction was permissive if the IVC was completely obstructed preoperatively, but it may also be considered in cases where the IVC is not completely obstructed.

Investigation of Major Genetic Polymorphisms in the Renin-Angiotensin-Aldosterone System in Subjects with Young-Onset Hypertension Selected by a Targeted-Screening System at University

Although polymorphisms in renin-angiotensin-aldosterone (RAA) system genes for angiotensinogen (AGT M235T), angiotensin-converting enzyme (ACE I/D), angiotensin II type 1 receptor (AT1 A/C1166), and aldosterone synthase (CYP11B2–344T/C) have been major targets for genetic investigation in association with essential hypertension (EH), the influence of these genetic factors is still to be determined. Because patients with young-onset EH are thought to possess a stronger genetic background than EH patients who show elevated BP relatively late in life, the targeted screening of hypertensive students in Tohoku University was completed for the selection of subjects for genetic investigation. Out of 16,434 students (12,794 males and 3,670 females) younger than 30, 22 students showed a high blood pressure (BP) (systolic and diastolic BP of 140 and/or 90 mmHg or greater, respectively, on two occasions and more than 135 and/or 85 mmHg, respectively, at a third measurement during casual BP measurements at the Tohoku University Health Center. These 22 students were asked to measure their BP at home (HBP). Six of the students had a systolic HBP of more than 135 mmHg and/or a diastolic HBP of more than 85 mmHg, and these students subsequently received medical examinations at Tohoku University Hospital and were diagnosed with EH. Genotyping for the four major genetic polymorphisms mentioned above was performed on the six students with EH and on 12 of the remaining 16 students whose HBP was within the normal range (white coat hypertension: WCH). Neither the EH nor the WCH students showed a different distribution of genotypes and allelic frequencies, compared to those found in the general Japanese population. Hence, the present study suggests that none of the major genetic polymorphisms in the RAA system strongly influence the onset of EH.

Characteristics of Young-Onset Hypertension Identified by Targeted Screening Performed at a University Health Check-Up

Since the prevalence and clinical characteristics of young-onset hypertension are still to be elucidated, we performed targeted-screening at an annual university health check-up for two consecutive years. Out of 16,464 subjects in 2003 and 17,032 in 2004 that were aged less than 30 years, 22 and 26 students (all males) exhibited high blood pressure (BP), respectively, on three occasions during casual BP measurements at the Tohoku University Health Center (systolic and diastolic BP of 140 and/or 90 mmHg or greater, respectively). These students were asked to measure their BP at home, and 9 subjects in total were diagnosed as having essential hypertension (EH). The remaining students were diagnosed as having white coat hypertension (WCH). In 8 out of 9 EH students, their father and/or mother had also been treated with antihypertensive medication. Adjustment by attendance ratio for each BP measurement suggested that the incidence of EH was around 0.1% and that of hypertension (EH and WCH) was around 0.5% in university students aged less than 25 years, since most of the subjects and hypertensive students were between 18 and 24 years old. Body mass index of the EH, which was more than 25 kg/m2 (overweight), was significantly higher than that with WCH. In conclusion, the combination of repeated casual BP measurements and home BP effectively identified young-onset EH. The clinical parameters indicated that male gender, genetic background, and excessive weight were risk factors for young-onset hypertension.

Transient Body Fluid Accumulation and Enhanced NKCC2 Expression in Gerbils with Brain Infarction

Background: Enhanced expression of a kidney-specific sodium co-transporter (NKCC2: Na-K-2Cl co-transporter) in the thick ascending limb of Henle has been identified in rat models of congestive heart failure and liver cirrhosis, suggesting that high NKCC2 expression underlies edema formation. An increased abundance of NKCC2, however, has also been noted in rats with the syndrome of inappropriate secretion of antidiuretic hormone; hyponatremia without edema. In the present study, we examined NKCC2 expression in non-edematous disease, such as a brain infarction, and investigated the physiological and/or pathological characterization of NKCC2 expression. Methods:We initially examined NKCC2 expression in an animal model of brain infarction. Mongolian gerbils (around 60 g body weight) underwent bilateral clamping of the common carotid arteries for 5 min for the induction of brain infarction. NKCC2 and apical water channel (AQP2) protein levels in the collecting duct were examined by Western blotting in kidney tissues 2, 7, and 14 days after the brain infarction. Gerbils with brain infarction were then fed either a normal low-sodium diet (0.3 g/kg/day) or a high-sodium diet (3.0 g/kg/day), and body weight, urine volume and urinary osmolality were examined daily. Blood parameters were measured on day 14 after the brain infarction. Results: Histochemical examination of the brain confirmed the presence of brain infarction, as manifested by altered cresyl violet staining in the hippocampus. Protein levels of NKCC2 were significantly increased in gerbils with brain infarction on days 2 and 7 after brain infarction, whereas AQP2 protein signals remained unaltered. However, the increased NKCC2 intensity disappeared on day 14. Body weight gain was slightly, but significantly greater in gerbils with brain infarction than in sham-operated gerbils up to 7 days after the brain infarction. The high-sodium diet resulted in significant urinary concentration and enhanced weight gain in infarcted gerbils. Conclusion: We noted increased NKCC2 abundance in non-edematous disease, which enhanced body fluid accumulation, likely via the sodium loading-dependent concentration of the urine. These results suggest that the physiological process of edema formation is based on specific NKCC2 expression. The transient duration of these findings in the present animal model suggests two different characteristics of specific NKCC2 expression, an immediate, transient appearance as a common response in serious conditions and more chronic expression that leads to edema formation.

Inhibitory Effects of a Biodegradable Gelatin Hydrogel Sponge Sheet on the Progression of Experimental Abdominal Aortic Aneurysms

We investigated the effects of a biodegradable gelatin hydrogel sponge sheet (GHSS) or GHSS incorporating basic fibroblast growth factor (GHSS + bFGF), which could prolong the effects of bFGF, on the progression of experimental abdominal aortic aneurysms (AAAs). Experimental AAAs were induced in male Sprague-Dawley rats by intra-aortic elastase infusion. The rats were divided according to the following treatments: (1) untreated, (2) GHSS alone, (3) GHSS incorporating 100 ng, 1 microg, and 10 microg of bFGF. GHSSs were placed over the elastase-infused aortas. After 14 days, the GHSS alone group and the three groups with GHSS + bFGF demonstrated significantly smaller aortic diameters than the untreated group, and these groups significantly attenuated a reduction of the elastic fibers and smooth muscle cells in the pathological findings. However, no additional therapeutic effect was noted between the GHSS alone and GHSS + bFGF groups. Immunohistochemical analysis revealed an increase of positive cells for endogenous bFGF in the media and adventitia of both the GHSS alone and GHSS + bFGF groups in comparison to the untreated group. In conclusion, GHSS itself possessed significant therapeutic effects on AAA progression by inducing the production of endogenous bFGF, leading to the preservation of elastic fibers and smooth muscle cells.

Steroid resistance in prolonged type I membranoproliferative glomerulonephritis and accelerated disease remission after steroid withdrawal

Two cases of severe proteinuria and hypocomplementemia were referred to our out patient clinic for continuous follow-up. Initial onset of clinical symptoms was at the age of 15 years in both cases. They had already been diagnosed as type I membranoproliferative glomerulonephritis (type I MPGN) by renal biopsy when oral prednisolone administration had been initiated. Several courses of steroid pulse therapy were performed for the flares of the disease, resulting in only temporary amelioration of renal symptoms. Percutaneous renal biopsy was performed during admission on both cases, showing severe glomerular and tubulointerstitial damages, in addition to typical type I MPGN findings such as mesangial cells and matrix interposition and subendothelial deposits. Because the continuous administration of steroid for more than 10 years did not ameliorate the clinical symptoms, steroid was markedly reduced or stopped in these cases. Such withdrawal from steroid therapy accelerated the amelioration of renal symptoms, including decrease in proteinuria, elevation of plasma protein and complement levels, and disappearance of generalized edema. The clinical courses of these cases indicate clinical choice of withdrawal from steroid therapy as one of the treatments in prolonged type I MPGN, which presents in childhood and shows steroid resistance.

Oral Steroid Use and Abdominal Aortic Aneurysm Expansion : Positive Association

BACKGROUND The maximum axial diameter (MAD) of a fusiform abdominal aortic aneurysm (AAA) is an indicator of the risk of expansion or rupture. Apart from smoking and MAD itself, few expansion risk factors have been reported. In this study, we investigated expansion risk factors for AAA.Methods and Results:This retrospective cohort study included 176 patients who attended Tohoku University Hospital with infrarenal fusiform AAA. AAA expansion rate was determined on multidetector computed tomography, and the correlations between expansion rate and the clinical data were analyzed. The median expansion rate was 2.405 mm/year. On univariate analysis, a significant positive correlation with expansion rate was observed for the initial MAD (P<0.001) and significant negative correlations for oral angiotensin receptor blocker usage (P=0.025), height (P=0.005), body weight (P=0.017), total cholesterol (P=0.007), low-density lipoprotein cholesterol (P=0.004), and HbA1c (P=0.037). On logistic regression analysis, significant positive associations with expansion rate were observed for initial MAD (P<0.001) and oral steroid usage (P=0.029) and a negative association for height (P=0.041). CONCLUSIONS Oral steroid usage is an important risk factor for AAA expansion, independent of other risk factors of atherosclerosis and MAD.