In many human cancers, tumorigenic potential is not equally shared by all cells but is restricted to phenotypically distinct subpopulations termed cancer stem cells. Cancer stem cells are also capable of both self-renewal and differentiation, and these functional properties have been suggested to play major roles in tumor initiation and progression. The factors responsible for the development of cancer stem cells and their subsequent regulation are unclear, but several chronic inflammatory states have been associated with an increased risk of malignancy. Therefore, it is possible that specific processes associated with chronic inflammation, as well as the adaptation to cellular stress, regulate cancer stem cells. Several factors associated with chronic inflammation, including cytokines, oxidative stress, and hypoxia, induce the activation of specific cellular response programs that can affect the survival, proliferation, metabolism, and differentiation of cancer cells, as well as the self-renewal and quiescence of normal stem cells. In this review, we discuss how these adaptive processes potentially become subverted to enhance the development and function of cancer stem cells.

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Background/Aims: Preventing internal hemorrhage extends the lifespan of rats with chronic bile duct ligation (CBDL), a common animal model of portal hypertension. We investigated hemodynamics during the early and late stages of cirrhosis caused by CBDL. We also evaluated the hemodynamic influence of NO, which is the chief vasodilator in hyperdynamic syndrome, by administration of an NO synthase inhibitor (N^G-nitro-L-arginine methyl ester: L-NAME; 10 mg/kg).
Animals/Methods: In 24 Sprague-Dawley rats (9 sham rats and 15 CBDL rats), hemodynamics were assessed under conscious and unrestrained conditions 4 and 8 weeks after surgery. Before and 30 minutes after L-NAME administration, the cardiac index (CI) and regional blood flow were measured with the reference sample method using ¹⁴¹Ce- and ¹¹³Sn-microspheres (15 μm in diameter).
Results: A hyperdynamic systemic circulation and splanchnic hyperemia were observed after CBDL, and these changes increased with the progression of cirrhosis. L-NAME significantly diminished the hyperdynamic circulation and also reduced splanchnic hyperemia. In 4-week CBDL rats, a low hemoglobin concentration made an important contribution to the hyperdynamic circulation, and the portal collateral system collapsed when inflow to the portal territory was reduced by L-NAME treatment. In 8-week CBDL rats, systemic hemodynamics were closely linked to both the splanchnic circulation and the renal circulation before and after L-NAME administration, apart from hepatic artery blood flow.
Conclusion: The distinctive hemodynamic changes of portal hypertension were found in 8-week CBDL rats. Thus, 8-week CBDL rats may be a better animal model of human portal hypertension than 4-week CBDL rats.

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Background: Coronary artery bypass grafting (CABG) is a highly successful treatment for prolonging the lives of selected patients; however, preoperative and postoperative renal dysfunction has been an important predictor of adverse cardiovascular events. Concerns have recently grown regarding chronic kidney disease (CKD), which is an independent risk factor for cardiovascular diseases. In the present study we examined the significance of renal function on the basis of the estimated glomerular filtration rate (eGFR) and analyzed other factors as predictors of long-term clinical outcomes after CABG.
Methods: The subjects were 195 patients who underwent CABG from July 1996 through September 2008 at our hospital. Patients who received preoperative dialysis or who died during hospitalization or both were excluded. The patients were divided into 2 groups based on eGFR at the time of discharge (eGFR ≥60 mL/min/1.73 m²: non-CKD group; or eGFR <60 mL/min/1.73 m²: CKD group), and long-term outcomes were compared between the groups. The effects of other risk factors on long-term morbidity and mortality were also examined.
Results: The mean age of patients was 64.6 ± 9.3 years, and the mean duration of follow-up was 69.5 ± 44.5 months. There were no significant differences in either deaths from all causes or cardiovascular deaths between the CKD group and the non-CKD group. Multivariate analysis using the Cox proportional hazards model revealed that age (hazard ratio, 1.044; p=0.001) was a predictor of all-cause death and that age (hazard ratio, 1.154; p<0.001), diabetes mellitus (hazard ratio, 3.122; p=0.046), unstable angina (hazard ratio, 5.012; p=0.003), and proteinuria (hazard ratio, 7.982; p<0.001) were predictors of cardiovascular death.
Conclusions: Our study demonstrates that age, diabetes mellitus, unstable angina, and proteinuria are factors that affect long-term prognosis after CABG, whereas eGFR <60 mL/min/1.73 m² is not a predictive risk factor for either all-cause death or cardiovascular death. Although the predictive value of eGFR <60 mL/min/1.73 m² is generally accepted, analysis of our own data with receiver operating characteristic curves shows that eGFR <50 mL/min/1.73 m² is a more sensitive predictor of long-term outcome.

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A basic study using animal models was performed to investigate whether the sciatic nerve retains physiological functions and normal morphology after the gradual elongation associated with adjacent bone elongation. Electrophysiological and histological studies were performed on the elongated sciatic nerve of rabbit accompanied by the femur bone elongation. Compound action potentials evoked by electrical stimulation of the sciatic nerve were recorded and histological specimens of elongated nerve fibers were obtained immediately after final bone elongation from 4 rabbits (immediate group). Three rabbits were allowed to recover for 8 weeks after the bone elongation (maintained group). Three rabbits without bone elongation were used as controls of the immediate and maintained groups (control group). In the immediate group, the average amplitude of evoked nerve potentials were 30.38 ± 1.58 mV before elongation and diminished significantly to 18.35 ± 1.25 mV immediately after elongation (P<0.01). The amplitude of evoked potentials was not significantly different between before (30.30 ± 0.61 mV) elongation and after elongation (27.47 ± 1.63 mV) in the maintained group. The axonal area of the myelinated nerve fibers of the proximal region of the sciatic nerve in the immediate group was significantly decreased after elongation (P<0.01). The decrease in the area of the distal region was greatest in the control group and was followed by that in the maintained group and the immediate group (P<0.05, 0.01). These results suggest that the sciatic nerve shows dysfunction immediately after elongation, but can recover electrophysiologically and histologically several weeks after elongation.

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Streptococcus pyogenes, or group A Streptococcus (GAS), causes superficial infections of the upper respiratory tract that manifest as diseases such as pharyngitis and tonsillitis. T serotypes, emm genotypes, and the antimicrobial susceptibility of GAS isolated from the pharynges of patients with pharyngitis and tonsillitis were studied. The two most common T serotypes were T12 (10/25: 40%) and T1 (7/25: 28%), and the two most common emm genotypes were emm12 (12/27: 44%) and emm1 (7/27: 26%). Good correlation was observed between these T serotypes and emm genotypes.

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Because multiple intracranial aneurysms are not rare, accurate preoperative detection of asymptomatic aneurysms is important. In this paper, we report a ruptured distal anterior cerebral artery (DACA) aneurysm associated with an unruptured mirror-image aneurysm in a 62-year-old man presenting with headache. Although delayed vasospasm after subarachnoid hemorrhage has been reported to persist for 2 to 3 weeks, angiographic parent artery narrowing was far more prolonged in our case. Computed tomography revealed a subarachnoid hemorrhage in the interhemispheric and right sylvian fissures and a right frontal lobe hematoma. Digital subtraction angiography demonstrated bilateral symmetric saccular aneurysms of DACAs. On the day of admission, both aneurysms were clipped using an interhemispheric approach in a one-stage procedure, and the hematoma was aspirated. Angiography performed 8 days after the surgery demonstrated a residual aneurysm neck on the left side. Follow-up digital subtraction angiography performed on day 42 from onset showed resolution of the residual aneurysm neck along with narrowing of the left A2. However, at 7 months, the A2 narrowing had lessened. The location of the bilateral aneurysms near the midline facilitated a single approach but necessitated the application of juxtaposed clips. Regarding the pathogenesis of the bilateral aneurysms, previous reports have suggested symmetry of congenital anatomic defects and hemodynamic stress as potential causes. The persistent narrowing that was observed could have resulted from proliferative vasculopathy or from fibrosis possibly induced by the clips.

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Reversible posterior leukoencephalopathy syndrome (RPLS) is induced by acute cerebral edema. Its symptoms include seizures, headache, altered mental status, and visual disturbances. The clinical and radiological findings are usually transient. This report describes a case of RPLS resulting in bilateral total blindness. A 40-year-old man presented with lethargy and bilateral visual loss. He had a 20-year history of hypertension, but had never been treated. On presentation, the left eye was able to perceive light, but the right eye was not. Radiological examination showed diffuse edema in the brain, and ocular fundus examination revealed severe bilateral hypertensive retinopathy. Antihypertensive therapy improved the patient's general condition, including blood pressure. Radiological findings 5 months later showed resolution of most of the abnormal signal areas. However, total blindness had developed in both eyes by day 15, and two courses of pulsed corticosteroid therapy failed to restore the visual loss.

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We describe a patient in whom a fish bone penetrated the duodenum and migrated into the right renal vein. The bone was successfully removed with surgery. The 75-year-old man was admitted to Nippon Medical School Tama Nagayama Hospital because of right upper abdominal pain persisting for 7 days. The patient's medical history was not relevant to the current disorder. Plain radiography showed no abnormalities. Computed tomography revealed a linear object of high intensity that had penetrated the duodenum and migrated into the right renal vein with thrombus. The object was surrounded by a low-density area, suggesting severe inflammation. The patient had eaten fish 1 day before the onset of abdominal pain. We diagnosed duodenal penetration caused by an ingested fish bone. Endoscopic examination showed erosion, but no fish bone or ulceration was detected in the duodenum. The patient was treated conservatively with fasting, peripheral parental nutrition, and intravenous antibiotics. Three days after admission, non-contrast-enhanced computed tomography showed no movement of the foreign body. The patient continued to have pain, and the decision was made to surgically explore the abdomen. Intraoperative ultrasonography showed that the foreign body had migrated completely into the right renal vein with thrombus. Severe inflammation of the right renal vein was observed. Because we could not remove the foreign body without seriously injuring the right renal vein, right nephrectomy was performed. Macroscopic examination of the surgical specimen confirmed the presence of a fish bone with thrombus in the right renal vein. The patient was discharged 9 days after operation, with no complications.

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We report a case of xanthogranulomatous cholecystitis (XGC) that was diagnosed preoperatively by means of ultrasonography (US) with the contrast-enhancement agent Sonazoid after a false-positive result had been obtained with fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET). A 69-year-old woman was admitted because of right upper quadrant pain. Blood tests revealed a serum CA19-9 level of 749.8 IU/L. Computed tomography (CT), US, and magnetic resonance imaging of the abdomen showed abnormal thickening of the gallbladder wall but no stones. The border between the gallbladder and the liver was unclear. FDG-PET revealed a lesion with increased uptake of tracer in the gallbladder wall. The thickness of the lesion was similar to that on CT. We suspected gallbladder carcinoma with hepatic invasion. To confirm the tentative diagnosis, we performed US with the contrast-enhancement agent Sonazoid. The gallbladder wall was homogeneously enhanced in the early vascular phase and remained enhanced for 90 seconds. Enhancement of the gallbladder wall was smooth and regular. The border between the gallbladder and liver was clear and smooth. On the basis of these examinations, we diagnosed chronic cholecystitis (XGC suspected), not gallbladder carcinoma. At surgery, the gallbladder wall was observed to be extremely thick because of severe inflammation, and cholecystectomy was performed. XGC was diagnosed on intraoperative pathological examination. Histopathological examination showed XGC, severe proliferative fibrosis with formation of multiple yellow-brown intramural nodules, and foamy histiocytes without malignant cells. In conclusion, the present case of XGC was diagnosed preoperatively with contrast-enhanced US after a false-positive result had been obtained with FDG-PET. Contrast-enhanced US can thus play important roles in diagnosing gallbladder disease and selecting treatment.

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We describe a 54-year-old man in whom esophageal carcinoma was diagnosed and who underwent video-assisted thoracoscopic surgery of the esophagus (VATS-E) in the prone position. Initially, the patient was fixed in a semiprone position, from which he could be rotated to a prone or left lateral position. Four ports were inserted, and then the patient was rotated to the prone position. Once the patient was prone, gravity caused the lung to move downwards. Next, the chest cavity was inflated with a CO₂ insufflation pressure of 6 mm Hg. Esophagectomy was then performed, and the lymph nodes in the middle and lower mediastinum and along the right recurrent laryngeal nerve were dissected. In the left upper mediastinum, lymph node dissection was performed after the residual esophagus was stripped. Stripping of the residual esophagus created sufficient working space and a clear operative field for lymph node dissection. VATS-E in the prone position has achieved remarkable results in Japan. It allows a clear operative view of the middle and lower mediastinum, but the working space in the upper mediastinum is limited. Our results indicate that esophageal stripping in prone VATS-E allows for safe and straightforward lymph node dissection along the left recurrent laryngeal nerve. Our technique overcame the difficulties usually encountered with this type of lymph node dissection.

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