Radiotherapy for lymph node metastases in patients with hepatocellular carcinoma: retrospective study

AIM: This study was conducted to evaluate the effect of external radiation therapy on lymph node metastases from hepatocellular carcinoma (HCC). METHODS: A total 28 patients with cytopathologically proven HCC were subjected to radiation therapy over a 5-year period, and treatment was continued in all cases. All patients underwent irradiation with a total dose ranging between 46 and 60 Gy in daily 2.0-Gy fractions, five times a week. RESULTS: Among the metastatic lesions treated, 18 (64%) and five (18%) patients achieved partial responses and complete responses, respectively. The 1- and 2-year overall survival rates and the median survival time were 53% and 33%, respectively, and 13 months in patients given external beam radiation therapy (EBRT) for a non-palliative, near-cure intent (n = 21). CONCLUSIONS: Although lymph node metastasis from HCC is sensitive to EBRT, the intent of EBRT should be limited to palliation. For palliative purposes, it is useful in treatment with 50 Gy in 25 fractions for these patients.     

Low-dose oral methotrexate for the management of childhood Cogan’s syndrome: a case report

Cogan’s syndrome is a rare inflammatory disease characterized by nonsyphilitic ocular interstitial keratitis associated with hearing loss and vestibular impairment. Although systemic corticosteroids are usually used as the standard therapy, hearing ability in most cases gradually deteriorates. We, herein, describe a patient with childhood Cogan’s syndrome who was treated with low-dose oral methotrexate, which successfully helped to taper the doses of the systemic corticosteroids. The serum levels of the complements were good markers for the disease activity in this patient.     

Lymphoepithelioma-like carcinoma of the esophagus: report of a case with non-progressive behavior

Lymphoepithelioma-like carcinoma (LELC) of the esophagus is extremely rare and the prognosis has been described to be favorable. Herein, the case is reported of esophageal LELC showing non-progressive course for 1 year. The patient was a 70-year-old Japanese man with a submucosal tumor in the lower esophagus. The tumor was endoscopically regarded as a benign leiomyoma. One year after the first endoscopic examination, the size of the lesion remained unchanged despite no treatment. Histologically, the tumor showed undifferentiated carcinoma associated with dense lymphocytic and plasma cell infiltration. Lymphoid follicles surrounded the tumor cell nests. Immunohistochemically, Ki-67 labeling index of the tumor cells were 76.0%, and there were few single-strand DNA-positive apoptotic cells. In situ hybridization using a digoxigen-labeled Epstein-Barr virus (EBV)-encoded small RNA (EBER)-1 riboprobe failed to detect the presence of EBV infection. Physicians should be aware that esophageal LELC endoscopically mimics benign submucosal tumor. This case may demonstrate that esophageal LELC is a slow-growing tumor and it is related to immune reaction.     

Olmesartan ameliorates renovascular injury and oxidative stress in Zucker obese rats enhanced by dietary protein

BACKGROUND: The metabolic syndrome is a risk factor for the development of renal and vascular complications. Dietary protein intake aggravates renal injury in Zucker obese rats, a model of the metabolic syndrome. This study investigated whether dietary protein intake enhances renal and vascular injuries by oxidative stress, and assessed effects of olmesartan, an angiotensin II type 1 receptor blocker, in this model. METHODS: Zucker obese rats were fed either a standard protein diet, high protein diet (OHP), or high protein diet containing olmesartan or hydralazine for 12 weeks. We examined the glomerulosclerosis score, endothelium-dependent relaxation response in the aorta, 4-hydroxy-2-nonenal (HNE) contents in the kidney and aorta, and mRNA expression of NAD(P)H oxidase components (p22phox and p47phox) in the renal cortex. RESULTS: The OHP rats developed proteinuria, glomerulosclerosis, and endothelial dysfunction. Olmesartan prevented the development of all these damages in OHP rats, whereas hydralazine improved only glomerulosclerosis. The high protein diet also augmented HNE accumulation in glomeruli, renal arteries, and aortas, and increased the mRNA expressions of p22phox and p47phox in the renal cortex in obese rats. Olmesartan, but not hydralazine, inhibited all these changes. CONCLUSIONS: These results suggested that increased dietary protein intake exacerbates renal and vascular injuries, and augments oxidative stress in a rat model of the metabolic syndrome. Olmesartan ameliorated these injuries, presumably through its antioxidative effects, whereas hydralazine improved only glomerulosclerosis through its antihypertensive action. Dietary protein-enhanced injuries in the metabolic syndrome may be associated with hypercholesterolemia and the activated renin-angiotensin system.     

Influence of cilnidipine or nisoldipine on sympathetic activity in healthy male subjects

The aim of this study was to investigate whether cilnidipine, an N- and L-type calcium channel blocker, and nisoldipine, an L-type calcium channel blocker, have different effects on sympathetic activity, using an identical group of healthy male subjects. Eight healthy men (22–28 years) were given 10 mg of cilnidipine or 10 mg of nisoldipine in a randomized crossover design. In each trial, in subjects without medication on day 1 (control) and with medication on day 2, we measured heart rate (HR), low frequency (LF)/high frequency (HF) of HR variability, and plasma noradrenaline (NA) in a resting supine position and during head-up tilt, and palmar sweating during a mental arithmetic test, before and at 1, 2, 4, 6, and 8 h after administration. Time-plasma concentration profiles of the two drugs were similar. Measurements in controls on the two days showed no significant difference in any of these parameters. Nisoldipine, but not cilnidipine, slightly increased HR and LF/HF at rest. Head-up tilt increased HR, LF/HF, and plasma NA. As evaluated with repeated-measures analysis of variance, head-up tilt induced a significant increase in LF/HF, but not HR or plasma NA, and the effect of cilnidipine was significantly less than that of nisoldipine (P = 0.017). Postural hypotension was not observed. There was no difference in mental arithmetic-induced sweating between the two drugs. Cilnidipine, but not nisoldipine, might have a weak inhibitory effect on reflex sympathetic activity.     

Aortic root subadventitial hematoma

A 51-year-old woman was operated on for aortic valve regurgitation 3 months after experiencing chest tightness awakening her from sleep. Intraoperative findings included turbid dark brown pericardial fluid and a nipple-shaped protrusion on the external aspect of the noncoronary sinus of Valsalva. Histologically, the lesion was enclosed by intact media and adventitia, and represented an organized hematoma. Dilated venules noted adjacent to the lesion were suggestive of an intramural hemangioma. The etiology of this lesion is unclear, but it might be an unusual type of intramural hematoma (IMH) and gives us a hint of an origin of IMH.     

Toxoplasmosis encephalitis following severe graft-vs.-host disease after allogeneic hematopoietic stem cell transplantation: 17 yr experience in Fukuoka BMT group

Toxoplasmosis is a rare but rapidly fatal complication that can occur following hematopoietic stem cell transplantation (HSCT). Over a 17-yr period at our institutions, a definite diagnosis of toxoplasmosis was made in only two of 925 allogeneic HSCT recipients (0.22%) and none of 641 autologous HSCT recipients. These two patients received a conventional conditioning regimen followed by transplantation from an HLA-matched donor; however, they developed severe graft-vs.-host disease, which required intensive immunosuppressive therapy. Despite prophylactic treatment with trimethoprim/sulfamethoxazole, their immunosuppressive state, as indicated by a low CD4(+) cell count, might have resulted in toxoplasmosis encephalitis. Rapid and non-invasive methods such as a polymerase chain reaction (PCR) test of their cerebrospinal fluid for Toxoplasma gondii and magnetic resonance imaging of the brain were useful for providing a definitive diagnosis and prompt therapy in these patients: one patient stabilized and survived after responding to treatment with pyrimethamine/sulfodiazine whereas the other died of bacterial infection. In addition, retrospective PCR analyses of the frozen stored peripheral blood samples disclosed that detection of T. gondii preceded the onset of disease, indicating routine PCR testing of peripheral blood specimens may be an early diagnostic tool. It should be noted that when patients receiving HSCT have an unexplained fever and/or neurological complications, PCR tests should be considered to avoid cerebral lesions and improve the outcome of the patients.     

Nicorandil suppresses the increases in plasma level of matrix metalloproteinase activity and attenuates left ventricular remodeling in patients with acute myocardial infarction

Nicorandil, a hybrid K_ATP channel opener and nicotinamide nitrate, reduces no-reflow phenomenon and improves cardiac function in patients with acute myocardial infarction (AMI). We repoted that nicorandil suppresses radical formation in patients with AMI undergoing primary percutaneous coronary intervention (PCI). In the present study, we tested the hypothesis that nicorandil treatment suppresses MMP activities and predicts ventricular remodeling in AMI. Sixty-two patients with AMI were randomized into nicorandil pretreatment (n = 31) and control (n = 31) groups after admission and underwent primary PCI. Nicorandil was administered as a bolus injection (4 mg) followed by constant infusion (8 mg/h) for 24 h just after admission. On days 1, 2, and 14 after the onset of AMI, the plasma levels of matrix metalloproteinase (MMP)-2 and MMP-9 were measured by enzyme-linked immunosorbent assay and the activities by gelatin zymography. There were no differences in the baseline clinical characteristics between the two groups. On day 1, there were no differences in both MMP-2 and MMP-9 levels and their activities between the two groups. However, both MMP-2 and MMP-9 levels and their activities were significantly lower in nicorandil than in control group on day 2 (MMP-2 level, 1 014 ± 39 vs 1 174 ± 44 ng/ml; MMP-9 level, 17 ± 1 vs 23 ± 2 ng/ml; both P < 005) and on day l4 (MMP-2 level, 970 ± 38 vs 1 221 ± 44 ng/ml; MMP-9 level, 17 ± 1 vs 23 ± 1 ng/ml; both P < 0.05). Left ventricular end-diastolic volume index (LVEDVI) at acute phase was not different between the two groups. At 6 months after AMI, LVEDVI was significantly smaller in nicorandil than in the control group (83 ± 4 vs 96 ± 4 ml/m², P < 0.05). The change in LVEDVI from acute phase to 6 months was positively correlated with MMP-2 and MMP-9 levels and activities. Nicorandil suppresses the increases in MMP levels and activities and prevents the development of ventricular remodeling in AMI.     

Acute coronary syndrome due to coronary thrombus formed by severe coronary spasm: a case report

A 47-year-old man was admitted to our hospital complaining of chest pain at rest in the early morning. Electrocardiography showed ST segment elevation in leads II, III and aVF. Emergency coronary angiography revealed total occlusion of the right coronary artery at the proximal portion. Intracoronary administration of isosorbide dinitrate successfully recanalized the right coronary artery. However, there was a thrombus image at the culprit lesion. Intracoronary administration of urokinase caused the residual thrombus to disappear completely. Follow-up coronary angiography at 1 week and 3 months revealed no organic stenotic lesion. Intravascular ultrasound showed only a little plaque without signs of ruptured plaque in the right coronary artery. Provocation coronary angiography revealed remarkable spasm causing total occlusion at the proximal portion of the right coronary artery. This case suggests that only severe coronary spasm without plaque rupture could form a thrombus causing acute coronary syndrome.     

Correlation between exercise electrocardiography test and coronary flow reserve in patients without organic coronary artery stenosis

OBJECTIVES: The exercise electrocardiography (ECG) test is frequently positive in patients without organic coronary artery stenosis. Although the reason for this false positive ST depression is not fully understood, one possibility may be related to coronary microvascular abnormality. The present study investigated the relationship between the exercise ECG test and coronary flow reserve (CFR) in patients with angiographically normal coronary arteries, but with positive ECG ST depression. METHODS: This study included 67 patients, 32 with chest pain syndrome, and 35 with vasospasm. The exercise ECG test was performed without drug administration in all patients, and the CFR was determined after diagnostic cardiac catheterization. RESULTS: Although a significant correlation was recognized between ST depression and CFR in patients with chest pain syndrome (p < 0.05), there was no correlation in patients with epicardial coronary vasospasm. CONCLUSIONS: In patients with chest pain syndrome, ST depression detected by the exercise ECG test may suggest coronary microvascular dysfunction. However, in patients with coronary vasospasm, ST depression may occur without decreased CFR, suggesting that coronary spasm or other mechanism (s) relating to ST changes are present during the exercise ECG test, and careful interpretation is needed.