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.     

Neuropathology of ALS: Spheroids

I briefly review spheroids observed in the anterior horns of the spinal cord in amyotrophic lateral sclerosis (ALS). Spheroids are argentophilic bodies more than 20 μm in diameter. Recently, some connections between the proximal axonal swellings including spheroids and the perikarya have been reported in some ALS patients with a short clinical course or mild depletion of anterior horn neurons. Most of the cell bodies directly connected with the axonal swellings appear normal, and spheroids are considered to be one of the hallmarks of the early histological changes in this disorder. Spheroids are strongly positive with anti-phosphorylated neurofilament antibody, and are also positive with calcitonin gene-related peptide and anti-peripherin antibody. Some spheroids are immunostained with anti-synaptophysin antibody and anti-ubiquitin antibody. Spheroids are not immunostained with anti-phosphorylated tau antibody, or high molecular weight microtubule associated proteins. Electron microscopically, spheroids are usually composed of densely packed accumulation of 10 nm neurofilaments with a variety of orientations, plus vesicles, dense bodies and mitochondria. When the swellings of the initial segment is relatively pronounced, the undercoating is obscured and the neurofilaments become interwoven in some parts. In the first internode of the myelinated axons, as the swellings become larger, the neurofilaments lose their parallel orientation and become intermingled. Large accumulation of neurofilaments resembling spheroids in the perikarya of large anterior horn cells suggests that spheroids could be derived not only from the axon including the proximal portion, but also from the perikarya. Structures apparently identical to axonal spheroids are observed at the light and electron microscopic levels in the proximal portion of axons of anterior horn cells in animal models intoxicated with β, β'-iminodipropionitrile (IDPN), or with aluminum, in hereditary canine spinal muscular atrophy (HCSMA). The pathogenetic mechanism is probably associated with an impairment in slow axonal transport which particularly affects the neurofilaments in IDPN and aluminum intoxication. Impairment of slow axonal transport of neurofilaments also plays an important role in the pathogenesis of ALS. The average diameter of even normalappearing initial segment is larger in ALS than in the controls. The perikarya connected with the swollen proximal axons and their dendrites almost always appear normal. These findings suggest that the slow axonal transport of neurofilaments is probably impaired in this portion of the axon at an early stage in ALS as well as animal models for human ALS. However, techniques to analyze slow axonal transport in humans still remain tobe developed. Recently, overexpression of neurofilament subunits in transgenic mice produces a condition resembling ALS. The transgenic model may offer an interesting perspective not only for testing therapeutic strategies but also for investigating in a systematic way the various genetic and environment factors controlling the onset and progression of the disease and might yield new insights on the etiology of ALS.     

Pitfalls in the surgical treatment of moyamoya disease. Operative techniques for refractory cases

Eleven cases of moyamoya disease refractory to indirect non-anastomotic revascularization, including encephalomyosynangiosis in two, encephaloduroarteriosynangiosis in seven, and encephalomyoarteriosynangiosis in two, are described. The patients suffered from recurrent cerebral ischemic symptoms, and further operative intervention, including superficial temporal artery-middle cerebral artery anastomosis and intracranial omental transplantation, was performed. The choice of operative maneuver depended on the availability of scalp arteries and on the nature of the ischemic symptoms. Although indirect non-anastomotic revascularization procedures have the advantage of technical ease and most patients respond to these procedures alone, there are some patients like the 11 presented here who are not cured by such procedures. In such cases, direct anastomotic revascularization is necessary for the prevention of stroke.     

Familial Mitochondrial Encephalomyopathy with Stroke-like Episodes and Episodic Disturbances of Consciousness: A Study of Pedigree Including Three Generations with Multisystemic Abnormalities

Abstract: We report here two cases in a family with pleomorphic clinical features which include mitochondrial myopathy, encephalopathy, stroke-like episodes, episodic disturbances of consciousness and other multisystemic abnormalities. The other signs observed in multisystemic abnormalities were ophthalmoplegia, short stature, diabetes mellitus, diabetes insipidus, renal dysfunction, optic atrophy, retinal degeneration, impairment of hearing and mental retardation or deterioration. A symptomatological variation was observed in cases in the same family. It is suggested that these widely varying symptoms may be expressions caused by a common biochemical defect which involves different tissuesin different individuals in the family. The syndromes observed in the present cases were compared with other possibly-related mitochondrial encephalomyopathies.     

Effects of Pyridoxalated Hemoglobin Polyoxyethylene Conjugate and Stroma-free Hemoglobin on Renal Vascular Responsiveness to Vasoactive Substances in Isolated Perfused Rat Kidney

Abstract: The effects of pyridoxalated hemoglobin polyoxyethylene conjugate (PHP) and stroma-free hemoglobin (SFH) on vascular responsiveness to various vasoactive substances were examined in isolated perfused rat kidneys. The kidneys isolated from rats were perfused with 6% PHP, 6% SFH, and 6% hydroxyethylstarch (HES) solution at a constant flow rate. Vascular responsiveness to acetylcholine (ACh), nitroglycerin (NG), norepinephrine (NE), and angiotensin-II (ANG-II) was examined by measuring the perfusion pressure (PP). Effects of inhibition of endothelium-derived relaxing factor (EDRF) by N^G-monomethyl L-arginine (L-NMMA) on NE-induced and ANG-II-induced renal vascular responses were examined. ACh and NG induced a dose-dependent decrease in perfusion pressure (PP) in all groups. NE and ANG-II induced an increase in PP in all groups, but NE-induced and ANG-II-induced responses in the PHP-perfused and SFH-perfused groups were significantly larger than those in the HES-perfused group. L-NMMA did not alter vascular responsiveness to NE and ANG-II. These results indicate that PHP and SFH do not inhibit EDRF induced by ACh, but hemoglobin moiety per se does augment the vascular responsiveness to NE and ANG-II in the isolated perfused rat kidney.     

Left ventricular diastolic dysfunction as assessed by echocardiography in metabolic syndrome.

The purpose of the present study was to elucidate the cardiac structure and function in patients who have metabolic syndrome but no history of cardiovascular disease by analyzing echocardiographic findings. Echocardiographic examination was performed to screen for cardiovascular disease in 135 patients who were in their sixties. Patients were divided into metabolic syndrome (n=65, age: 65+/-2.7 years) and non-metabolic syndrome (n=70, age: 66+/-2.5 years) groups based on the criteria for metabolic syndrome proposed by the Japanese Society of Hypertension and seven other societies in 2005. The left ventricular (LV) wall thickness and dimension were measured by M-mode echocardiography. The relative wall thickness, LV mass index, and LV ejection fraction (LVEF) were calculated. LV diastolic function was assessed by the peak velocity of early rapid filling (E velocity) and the peak velocity of atrial filling (A velocity), and the ratio of E to A (E/A) was assessed by the transmitral flow. The Tei index, which reflects both LV diastolic and systolic function, was also calculated. There were no differences in relative wall thickness, LV mass index, or LVEF between the two groups. However, both the EIA and Tei index were significantly different between the metabolic syndrome (0.66+/-0.14 and 0.36+/-0.07, respectively) and non-metabolic syndrome (0.88+/-0.25 and 0.29+/-0.09) groups (p<0.001). These results indicate that patients with metabolic syndrome can have cardiac diastolic dysfunction even if they have neither LV hypertrophy nor systolic dysfunction.     

Urinary dysfunction and autonomic control in amyloid neuropathy

Abstract Uro-neurological assessment was performed in four patients with small-fiber neuropathy due to amyloidosis (2 transthyretin-type/2 immunoglobulin light-chain-type). Voiding difficulties were due to detrusor weakness and impaired bladder sensation. In two patients cholinesterase inhibition treatment caused urge incontinence, indicating detrusor denervation supersensitivity. The underlying mechanisms of urinary dysfunction seem to involve postganglionic cholinergic and afferent somatic nerves.     

Effects of blood coagulation factor XIII on the development of experimental cerebral aneurysms in rats

Pathological and experimental studies have shown that cerebral aneurysms develop in part as a result of injury to the blood vessel wall. One of the peculiar aspects of aneurysm development is a defective proliferative or healing response to such injury. To examine this phenomenon, blood coagulation Factor XIII, which is known to enhance the healing process of wounds in general, was given to rats to induce experimental cerebral aneurysms. The rats were subjected to ligation of one common carotid artery and induction of hypertension, and were fed beta-aminoproprionitrile. Two weeks thereafter, Factor XIII was injected intravenously daily for 5 days (10 U/100 gm body weight/day). Twelve days after the start of Factor XIII injections, the rats were sacrificed and examined under light and electron microscopy. In seven of 12 bifurcations which developed small aneurysms, prominent intimal thickening was observed in the aneurysm lumen. In the most advanced cases, the aneurysm lumen was completely filled with proliferated smooth-muscle cells and collagen. In five of nine bifurcations that showed no aneurysm development, apparent intimal thickening was found at the site where aneurysms might be expected to grow. In the group of rats studied for induction of cerebral aneurysms but not given Factor XIII, none of 11 bifurcations with or without aneurysms showed such intimal thickening. The results indicated that the proliferative response at the sites of aneurysm development was modified by exogenous Factor XIII.     

Treatment strategies for hepatic metastasis from colorectal cancer

Hepatic micrometastases of the parenchyma adjacent to a macroscopic lesion were detected in 17 of 31 resected liver metastases. Fifty-nine micrometastatic lesions were detected in total; 26 lesions were situated in the portal vein (PV), 22 in the central vein (CV), 5 in the bile duct (BD), and 6 in the sinusoid (SS). A histological study confirmed the direct invasion of the macrometastatic cancer cells into the adjacent PV, CV, BD, and SS. According to the tumor doubling time, the mean diameter of the macrometastases in 19 remnant livers was calculated to have been 0.57±0.87 cm at the time of the primary resection. The calculated diameter of 3 of these 19 macrometastases was found to be less than 0.01 cm, the minimum implantable size, indicating that the cancer recurrence in these specimens may have developed from macroscopic metastatic lesions as a satellite, and not from the primary tumor. In 13 patients who received doses of 5250 mg or more of 5 fluorouracil (FU) via the hepatic artery, the cumulative disease-free rate 2 years postoperatively was 100%; this value was 47.6% in 11 patients who received less than 5250 mg of 5 FU via the hepatic artery, and 0% in 39 patients who received no chemotherapy (P<0.005). These results suggest that anatomical hepatic resection for satellite lesions, combined with prophylactic hepatic arterial chemotherapy for micrometastases, decreases the recurrence rate of hepatic metastases in the remnant liver.