Surgical outcomes of nephron-sparing surgery for renal tumors

PURPOSE: We retrospectively assessed the surgical outcomes of nephron-sparing surgery (NSS) for patients with renal tumors. PATIENTS AND METHODS: From 1985 to March 2001, a total of 99 NSSs were performed on 94 patients with renal tumors. The patients were divided into three groups. Group I comprised of 22 patients who underwent imperative surgeries for renal cell carcinoma (RCC). The tumors were found in 18 patients bilaterally (including 8 patients with von Hippel-Lindau disease), in 3 with solitary kidney, and in 1 with chronic renal failure. The mean +/- standard deviation of patient age and tumor diameter was 46 +/- 23 years and 36 +/- 23 mm, respectively. Twenty-three in situ NSSs were performed on 18 patients in Group I, and the remaining 4 patients were treated with 3 simultaneous operations for bilateral renal tumors with or without 2 ex vivo surgeries. Group II consisted of 49 patients who had small RCCs with the normal contralateral kidney and underwent NSSs (elective indication). The mean age and tumor diameter was 54 +/- 10 years and 28 +/- 11 mm, respectively. Group III consisted of 23 patients with non-RCC tumor (10 angiomyolipomas, 8 cystic tumors, 2 adenomas, 2 metastatic tumors, and 1 degenerative lesion), all of whom were treated with NSS. The mean age and tumor diameter was 47 +/- 14 years and 41 +/- 29 mm, respectively. RESULTS: In Group I, 3 patients died of cancer including 2 patients who had had multiple lung metastases preoperatively. The five-year tumor specific survival rate was 87.3% with a postoperative follow-up of 49 +/- 36 months. In Group II, there were few peri-operative complications or no local recurrence at follow-up of 52 +/- 38 months. A patient developed lung metastasis, which was removed surgically with no evidence of recurrence at 159 months after NSS. Postoperative renal scintigraphy on 35 patients showed well-preserved renal function of the operated kidney. Improvement in surgical techniques resulted in less-invasive surgery in 22 operations during the last 4 years. The patients of Group III were also operated uneventfully, although 1 experienced postoperative bleeding. In 12 patients with solitary kidney (11 in Group I and 1 in Group III) serum creatinine level increased transiently, decreased to 1.3 times of preoperative values within 3 months, and almost recovered at 1-year follow-up. CONCLUSION: Excellent outcomes in cancer control and preservation of renal function support the validity of nephron-sparing surgery to treat renal tumors. The candidate patients may include those with bilateral kidney tumors, tumor occuring in the solitary kidney or small renal cell carcinomas with the normal contralateral kidney. Earlier detection of small lesions and less invasive surgical techniques will facilitate a wider indication of NSS.     

Bilateral carotid stenting for bilateral carotid artery stenosis improved vascular dementia

We report a case of bilateral internal carotid artery (ICA) stenosis treated with stenting. A 78-year-old man suffered from vascular dementia and left hemiparesis, and, by magnetic resonance angiogram (MRA), was diagnosed as having bilateral ICA stenosis. Cerebral angiogram showed severe, bilateral ICA stenosis (right; 88%, left; 93%) and xenon single photon emission tomography (SPECT) showed severely decreased cerebral blood flow (CBF) and cerebrovascular reactivity (CVR). We performed bilateral carotid angioplasty with self-expanding stents. Both CBF and CVR were improved bilaterally after the operation. The patient was discharged without neurological deficits. Carotid stenting may be an alternative treatment for severe ischemia caused by severe, bilateral ICA stenosis.     

Spinal cord compression due to extramedullary hematopoiesis associated with polycythemia vera--case report

A 69-year-old woman with a 14-year history of polycythemia vera suffered progressive paraparesis due to epidural involvement of hematopoietic tissue. Magnetic resonance (MR) imaging demonstrated extensive epidural masses. Decompressive surgery and radiotherapy were performed and she made an almost complete clinical recovery. Serial MR imaging showed no regrowth of the other epidural masses. Extramedullary hematopoiesis occurs in patients with various hematologic disorders involving a chronic increase in the production of red blood cells, and is often associated with thalassemia, but is less common with polycythemia vera. The most frequent sites are the spleen, liver, and kidney. Extramedullary hematopoietic tissue occurring within the spinal canal and causing cord compression is very rare. Total surgical excision is not usually feasible because of the diffuse nature of extramedullary hematopoietic tissue and the possibility of recurrence, but acute neurological deterioration does require emergency surgery. Extramedullary hematopoiesis is radiosensitive and displays a rapid response to low dosages, so radiation therapy is recommended for residual tumors. Considering the possibility of central nervous system extramedullary hematopoiesis in patients with polycythemia vera, an early diagnosis is necessary for a favorable prognosis.     

Peripheral small-sized (2 cm or less) non-small cell lung cancer with mediastinal lymph node metastasis; clinicopathologic features and patterns of nodal spread

Objective: The diagnosis of small-sized (2 cm or less) non-small cell lung cancer (NSCLC) has increased with the development of computed tomography (CT), whereas unexpected extensive multiple-level mediastinal involvement has been occasionally detected in this small-sized lung cancer. To establish the optimal surgical strategy, we retrospectively analyzed the clinicopathologic features, efficacy of preoperative investigations and lobe specific patterns of nodal spread in small-sized NSCLC with mediastinal involvement. Methods: Among 1550 resected lung cancer cases between 1981 and 2000, 267 (17.2%) had peripheral small-sized NSCLC. Of these, 29 patients (10.8%) with mediastinal lymph node involvement who underwent pulmonary resection and systematic nodal dissection were reviewed. Results: Among 29 patients, 27 patients (93.1%) were adenocarcinoma, and 51.7% (15/29) showed no lymph node enlargement on CT (cN0). Surgical pathology revealed multiple-level mediastinal involvement in 65.5% (19/29) of all patients and 60.0% (9/15) of cN0 patients. All of right upper lobe tumors (n=11) showed multiple-level involvement. Thallium-201 single photon emission computed tomography (201Tl-SPECT) was positive for increased focal uptake in the mediastinum in 72.7% (8/11) of patients. Conclusions: The vast majority of cases were adenocarcinoma, and two thirds of them showed multiple-level mediastinal involvement, even in cN0 patients. We thus recommend to perform systematic nodal dissection or meticulous sampling for accurate intrathoracic staging, especially for right upper lobe tumor. 201Tl-SPECT appears to be more sensitive preoperative investigation for mediastinal metastasis compared with CT scan.     

Relationship between sperm mitochondrial membrane potential,sperm motility,and fertility potential

AIM:To analyze the relationship between sperm mitochondrial membrane potential and sperm motility parameters by means of a computer-assisted sperm analyzer (CASA) and in-vitro fertilization rate(%FR). METHODS: Semen samples were obtained from 26 men undergoing in vitro fertilization-embryo transfer (IVF-ET). Informed consent was obtained from all men prior to the study. Samples were prepared using wash and swim-up method in HEPES-HTF medium. The sperm motility (%MOT), progressive motility (%PMOT), average path velocity (VAP) microm/s), straight line velocity (VSL) (micro m/s), curvilinear velocity (VCL) (microm/s) and %hyperactivated sperm (%HA), and the %FR were assessed. The samples were incubated in the presence of 2.0 mciromol/L of 5,5',6,6'-tetra-chloro-1,1',3,3'-tetraethylbenzimidazolyl-carbocyanine iodide (JC-1) for 30 min at 37 degrees C in air and washed in PBS before flow cytometry (FACSCalibur: Becton Dickinson) analysis. The mitochondrial probe JC-1 was used to identify the mitochondrial membrane potential. The sperm was divided into three populations according to the fluorescence pattern as follows: the high mitochondrial membrane potential group (n=8), the moderate group (n=5), and the low group (n=13). Statistical analysis was performed using unpaired t-test. RESULTS:Significant differences were found between the high and the low groups in %MOT (91.1+/-8.5 vs 63.0+/-32.7, mean+/-SD), VAP (73.0+/-14.2 vs 52.1+/-12.5), VCL (127.0+/-28.1 vs 87.0+/-22.6), %HA (27.3+/-23.6 vs 7.2+/-9.0) and %FR [73.2 (48/56) vs 59.0 (69/117)]. No significant differences were found in other CASA parameters. CONCLUSION: When the sperm mitochondrial membrane potential increases, sperm motility parameters and fertility potential will also increase. The JC-1 dye method is useful to predict sperm fertility potential.     

Regulation of ER molecular chaperone prevents bone loss in a murine model for osteoporosis

Endoplasmic reticulum (ER) stress response is important for protein maturation in the ER. Some murine models for bone diseases have provided significant insight into the possibility that pathogenesis of osteoporosis is related to ER stress response of osteoblasts. We examined a possible correlation between osteoporosis and ER stress response. Bone specimens from 8 osteoporosis patients and 8 disease-controls were used for immunohistochemical analysis. We found that ER molecular chaperones, such as BiP (immunoglobulin heavy-chain binding protein) and PDI (protein-disulfide isomerase) are down-regulated in osteoblasts from osteoporosis patients. Based on this result, we hypothesized that up-regulation of ER molecular chaperones in osteoblasts could restore decreased bone formation in osteoporosis. Therefore, we investigated whether treatment of murine model for osteoporosis with BIX (BiP inducer X), selective inducer BiP, could prevent bone loss. We found that oral administration of BIX effectively improves decline in bone formation through the activation of folding and secretion of bone matrix proteins. Considering these results together, BIX may be a potential therapeutic agent for the prevention of bone loss in osteoporosis patients.     

Antiobesity Effect of Eicosapentaenoic Acid in High-Fat/High-Sucrose Diet�CInduced Obesity: Importance of Hepatic Lipogenesis

OBJECTIVE

Given the pleiotropic effect of eicosapentaenoic acid (EPA), it is interesting to know whether EPA is capable of improving obesity. Here we examined the anti-obesity effect of EPA in mice with two distinct models of obesity.

RESEARCH DESIGN AND METHODS

Male C57BL/6J mice were fed a high-fat/high-sucrose diet (25.0% [w/w] fat, 32.5% [w/w] sucrose) (HF/HS group) or a high-fat diet (38.1% [w/w] fat, 8.5% [w/w] sucrose) (HF group) for 4–20 weeks. A total of 5% EPA was administered by partially substituting EPA for fat in the HF/HS + EPA and HF + EPA groups.

RESULTS

Both the HF/HS and HF groups similarly developed obesity. EPA treatment strongly suppresses body weight gain and obesity-related hyperglycemia and hyperinsulinemia in HF/HS-fed mice (HF/HS + EPA group), where hepatic triglyceride content and lipogenic enzymes are increased. There is no appreciable effect of EPA on body weight in HF-fed mice (HF + EPA group) without enhanced expression of hepatic lipogenic enzymes. Moreover, EPA is capable of reducing hepatic triglyceride secretion and changing VLDL fatty acid composition in the HF/HS group. By indirect calorimetry analysis, we also found that EPA is capable of increasing energy consumption in the HF/HS + EPA group.

CONCLUSIONS

This study is the first demonstration that the anti-obesity effect of EPA in HF/HS-induced obesity is associated with the suppression of hepatic lipogenesis and steatosis. Because the metabolic syndrome is often associated with hepatic lipogenesis and steatosis, the data suggest that EPA is suited for treatment of the metabolic syndrome.The metabolic syndrome has been defined as a cluster of visceral fat obesity, impaired glucose metabolism, atherogenic dyslipidemia (high plasma triglyceride and low HDL cholesterol), and hypertension (1). There is considerable evidence that visceral fat obesity is a key etiological factor in the metabolic syndrome (2). Enhanced hepatic lipogenesis and hepatic steatosis also appear to play an important role in the pathogenesis of the metabolic syndrome (3). Indeed, nonalcoholic fatty liver disease may constitute the common features of the metabolic syndrome.Numerous epidemiological studies and clinical trials have revealed that fish oil and n-3 polyunsaturated fatty acids (PUFAs) reduce the risk of coronary heart disease (4). Eicosapentaenoic acid (EPA), one of the major n-3 PUFAs contained in fish oil, has a variety of pharmacological effects such as lipid-lowering (5), anti-platelet (6), anti-inflammatory (7), and anti-atherogenic effects (8,9). Recently, the Japan EPA Lipid Intervention Study (JELIS), a large-scale prospective randomized clinical trial, demonstrated that EPA delays the onset of cardiovascular events via cholesterol-independent mechanisms (10,11), but the molecular mechanisms remain to be elucidated. In a recent sub-analysis of the JELIS, EPA had a great risk reduction of coronary artery events of 53% in patients with high triglycerides and low HDL cholesterol (11), suggesting that EPA may be effective to reduce the incidence of atherosclerosis in the metabolic syndrome. These findings are supported by our recent observations that EPA administration results in decreases in remnant-like particle-triglyceride, small dense LDL, and C-reactive protein and an increase in adiponectin in patients with the metabolic syndrome (12,13).Given the pleiotropic effect of EPA, it is interesting to know whether highly purified EPA is capable of improving obesity. There is currently a controversy as to the anti-obesity effect of EPA; it has been effective (13,14), has been ineffective (15), or has even increased visceral fat accumulation (16). On the other hand, it is noteworthy that EPA suppresses hepatic lipogenesis and steatosis by reducing mRNA and active protein of sterol regulatory element binding protein-1c (SREBP-1c) (17–19). We, therefore, examined the impact of hepatic lipogenesis on the anti-obesity effect of highly purified EPA.Here, we demonstrate that EPA strongly suppresses body weight gain and obesity-related hyperglycemia and hyperinsulinemia in high-fat (HF)/high-sucrose (HS)-induced obese mice with enhanced hepatic lipogenesis but not in HF-induced obese mice without enhanced hepatic lipogenesis. This study is the first demonstration that the anti-obesity effect of EPA is related to the suppression of hepatic lipogenesis. Given that the metabolic syndrome is often associated with hepatic lipogenesis and steatosis, the data of this study suggest that EPA is suited for the treatment of the metabolic syndrome.     

Surgical Intervention for Malignant Fibrous Histiocytoma of the Lung: Report of a Case

Malignant fibrous histiocytoma (MFH) of the lung is rare, accounting for less than 0.2% of all pulmonary neoplasms, and an optimal treatment strategy has not yet been elucidated. We encountered a 62-year-old male patient with MFH of the lung who underwent a resection of the lymph node of recurrence 7 months after a lobectomy. We herein review 93 cases of pulmonary MFH in the literature, and discuss the surgical treatment for this disorder with special reference to lymph node involvement. Lymphogenic metastasis was observed in 14 of 72 cases (19%) who underwent surgical treatment. The 5-year survival rates for these reported patients with and without surgical treatment were 43% and 0% (P = 0.01) and the 5-year survival rates for “resected” patients with and without lymph node metastasis were 27% and 49%, respectively (P = 0.03). A complete resection with the systematic dissection of regional lymph nodes is therefore considered to positively contribute to the survival of patients with primary pulmonary MFH.     

Intrathecal injection of epidermal growth factor and fibroblast growth factor 2 promotes proliferation of neural precursor cells in the spinal cords of mice with mutant human SOD1 gene

We investigated three steps of neural precursor cell activation--proliferation, migration, and differentiation--in amyotrophic lateral sclerosis spinal cord treated with intrathecal infusion of epidermal growth factor (EGF) and fibroblast growth factor 2 (FGF2) into the lumbar spinal cord region of normal and symptomatic transgenic (Tg) mice with a mutant human Cu/Zn superoxide dismutase (SOD1) gene. We observed that 5-bromodeoxyuridine (BrdU) + nestin double-labeled neural precursor cells increased in the spinal cords of Tg mice compared with non-Tg mice, with a much greater increase produced by EGF and FGF2 treatment. The number of BrdU + nestin double-labeled cells was larger than that of BrdU + ionized calcium-binding adapter molecule-1 (Iba1), BrdU + glial fibrillary acidic protein (GFAP), or BrdU + highly polysialylated neural cell adhesion molecule (PSA-NCAM) double-labeled cells, but none expressed neuronal nuclear antigen (NeuN). On further analysis of the gray matter of Tg mice, the number of BrdU + nestin and BrdU + PSA-NCAM double-labeled cells increased more in the ventral horns than the dorsal horns, which was again greatly enhanced by EGF and FGF2 treatment. Because neural precursor cells reside close to the ependyma of central canal, the present study suggests that proliferation and migration of neural precursor cells to the ventral horns is greatly activated in symptomatic Tg mice and is further enhanced by EGF and FGF2 treatment and, furthermore, that the neural precursor cells preferentially differentiate into neuronal precursor cells instead of astrocytes in Tg mice with EGF and FGF2 treatment.