Involvement of estrogen receptors in prostatic diseases

Accumulating evidence shows that estrogens participate in the pathogenesis and development of benign prostatic hyperplasia and prostate cancer by activating estrogen receptor α. In contrast, estrogen receptor β is involved in the differentiation and maturation of prostatic epithelial cells, and thus possesses antitumor effects in prostate cancer. However, the natural ligands of estrogen receptor β are not fully understood, and its mode of action according to its ligands and the binding sites located in the promoter regions of downstream genes remains to be elucidated. Here, we review recent experimental investigations of estrogen receptors and their urological relevance. Estrogen receptor‐mediated signaling in the prostate is essential together with the androgen receptor‐mediated pathway, providing a new therapeutic target for prostatic diseases.     

Effects of Sevoflurane and Isoflurane on Renal Function and on Possible Markers of Nephrotoxicity

Background: Low-flow sevoflurane anesthesia is associated with increasing circuit concentrations of compound A, which is nephrotoxic in rats, but the effect of compound A and low-flow sevoflurane anesthesia on renal function in humans is unclear. The authors compared the effects of high- and low-flow sevoflurane and isoflurane anesthesia on renal function and on several possible markers of nephrotoxicity in humans.

Methods: Forty-two patients without preexisting renal disease underwent either low-flow isoflurane (1 l/min, n = 14), low-flow sevoflurane (1 l/min, n = 14), or high-flow sevoflurane (6 l/min, n = 14) anesthesia for body-surface-area surgery scheduled to last at least 4 h. Twenty-four-hour urinary excretion of N-acetyl-[small beta, Greek]-glucosaminidase (NAG), [small beta, Greek]2-microglobulin, protein, glucose, blood urea nitrogen (BUN), and serum creatinine concentrations were measured before and after anesthesia.

Results: There were no differences in blood urea nitrogen, creatinine, and creatinine clearance among the three groups after anesthesia. Increased urinary N-acetyl-[small beta, Greek]-glucosaminidase excretions were seen in the low-flow and high-flow sevoflurane groups, but not in the low-flow isoflurane group (P < 0.01). Ten patients in the low-flow sevoflurane group had 24-h urinary excretion of protein that exceeded the normal ranges after anesthesia, but only one patient in the isoflurane and none in the high-flow sevoflurane groups had this.     

An emergent operation for metastatic cardiac tumor of malignant cystosarcoma phyllodes

A 47-year-old owman was transferred to our hospital under endotracheal intubation with severe hemodynamic deterioration. A left mastectomy had been performed 8 months earlier and histology of the specimen showed malignant cystosarcoma phyllodes. An angiography and echocardiography suggested massive mass of the right ventricle extending to the pulmonary artery. An emergent life-saving operation was required using cardiopulmonary bypass. A huge multilobular tumor was resected from the right ventricle through the pulmonary artery as much as possible and a tricuspid valvuloplasty was also performed. The patient was weaned from cardiopulmonary bypass, then satisfactorily recovered from hemodynamic disturbances. Nevertheless, she died 15 days later due to multiple organ failure. Microscopic examination of resected specimen showed the neoplastic stromal cells that increase mitotic activity and have sarcomatous characteristics, consistent with a metastatic cystosarcoma phyllodes. This is a second case of operation for cardiac metastasis of cystosarcoma phyllodes using cardiopulmonary bypass, so far presented in the literature of the world reviewed by the authors.     

Surgical Treatment for Biliary Carcinoma Arising After Pancreatoduodenectomy

The clinicopathological features and surgical treatment of biliary carcinoma around the major hepatic duct confluence arising after pancreatoduodenectomy (PD) due to initial bile duct carcinoma are described in three patients. Occurrence of biliary carcinoma more than 12 years after initial surgery and a histological finding of cholangiocellular carcinoma mixed with hepatocellular carcinoma suggested metachronous incidence of biliary carcinoma after PD. Extended right hemihepatectomy with complete removal of the residual extrahepatic bile duct and segmental, resection of the jejunal loop were carried out safely without operative death or severe postoperative complications. Two patients died of tumor recurrence 6 months after surgery, and the remaining patient is currently living a normal life without evidence of recurrence 17 months after surgery. These surgical procedures are a therapeutic option in patients with biliary carcinoma around the major hepatic duct confluence arising after PD.     

Stroke in surgery of the arteriosclerotic descending thoracic aortic aneurysms: influence of cross-clamping technique of the aorta.

OBJECTIVE: The risk of stroke caused by dislodgment of loose atheromatous plaque or mural emboli is increased by cross-clamping of the aorta. Some patients undergo descending thoracic aortic aneurysm repair with proximal aortic cross-clamping between the left common carotid artery and the left subclavian artery. The objective of this study was to determine the influence of proximal aortic cross-clamping in arteriosclerotic aneurysm or dissecting aneurysm repair. METHODS: Between May 1984 and May 2003, 81 patients underwent elective surgery for distal arch or descending aortic aneurysm repair with proximal aortic cross-clamping between the left common carotid artery and the left subclavian artery. To evaluate the influence of the proximal aortic cross-clamping, patients were divided into two groups: patients who had undergone arteriosclerotic aneurysm repair (group I, n=25) and patients who had undergone dissecting aneurysm repair (group II, n=56). RESULTS: Eight (9.9%) of the 81 patients had a stroke. Six strokes occurred in operations for arteriosclerotic aneurysm repair group I and two strokes occurred in operations for dissecting aneurysm repair group II (24 vs 3.6%; p=0.009). In-hospital mortality rates were 12% in group I and 8.9% in group II (p=0.70). Major postoperative complications included renal failure requiring hemodialysis (in 4.2% of the patients in group I and in 8.3% of the patients in group II, p=0.99) and pulmonary complication (in 20% of the patients in group I and in 16% of the patients in group II, p=0.67). CONCLUSION: Cross-clamping between head vessels should be avoided if at all possible when operating on patients who have arteriosclerotic descending thoracic aneurysms.     

Reversal of diabetes in pancreatectomized pigs after transplantation of neonatal porcine islets

Neonatal porcine islets (NPIs) are able to grow and to reverse hyperglycemia after transplantation in immunoincompetent mice. The aim of this study was to demonstrate the feasibility of allogeneic NPI grafts to achieve normoglycemia in a pancreatectomized diabetic pig. NPIs were isolated from pancreases of 1- to 3-day-old pigs, cultured, and then transplanted via the portal vein into the liver of totally pancreatectomized pigs (mean body weight, 20.8 kg). Each pig received NPIs consisting of 3.1 +/- 0.3 x 10(6) beta-cells/kg (12,476 +/- 1,146 islet equivalent/kg). The six pigs that were given cyclosporine and sirolimus achieved normoglycemia by day 14 without insulin therapy. Three pigs died of surgical complications shortly after transplantation, whereas the other three remained insulin independent up to day 69. Of seven nonimmunosuppressed recipients, four pigs became normoglycemic by day 14 without insulin treatment, with two of the animals remaining normoglycemic long term. Well-preserved insulin-positive cells were found in the graft at the end of follow-up with a significant increase in insulin content in long-term survivors of both groups. This study demonstrates for the first time that allogeneic NPIs can reverse hyperglycemia in totally pancreatectomized diabetic pigs.     

Experience from "double-insurance bypass." Surgical results and additional techniques to achieve complex aneurysm surgery in a safer manner

BACKGROUND: "Double-insurance bypass" was recently advocated to avoid the risk of cerebral ischemia during prolonged temporary occlusion of the carotid artery. For large aneurysms needing temporary but prolonged obliteration of the internal carotid artery (ICA). We have attempted the double-insurance bypass in 15 patients and, herein, report the efficacies and limitations of the procedure, and surgical techniques to make this procedure safer. METHODS: We treated 15 patients with complex internal carotid aneurysms by clipping surgery with the aid of radial artery (RA) to proximal middle cerebral artery (MCA) bypass, so-called double-insurance bypass. We analyzed surgical results of the procedure. RESULTS: In 11 patients, the duration of temporary occlusion of the ICA could be prolonged for as long as 110 minutes (mean, 45 minutes) without any ischemic complications. One patient in the earlier period of our experience suffered extended cerebral infarction due to possible restricted blood flow through the RA, because the brachial artery was compressed by the firm shoulder joint and neighboring structures. Thereafter, we routinely monitored the blood pressure of MCA (MCABP) and never experienced such cortical infarctions. Another 3 patients, however, experienced ischemia in the territory of perforating arteries that originated from a segment that could not be perfused by the RA-MCA bypass. CONCLUSIONS: In combination with monitoring of MCABP, the double-insurance bypass can be a safer and more potent adjunctive procedure for the treatment of complex internal carotid aneurysms which require prolonged temporary occlusion of the ICA.     

Intraluminal lavage to remove exfoliated tumor cells after colorectal endoscopic submucosal dissection

Background

Endoscopic submucosal dissection (ESD) involves dissection of tumors and manipulation of them in an exposed condition for prolonged periods. A large number of tumor cells are exfoliated into the intestinal lumen after colorectal ESD. The aim of this study was to determine whether lavage volume has an influence on tumor cell clearance after colorectal ESD.

Methods

Twenty patients who underwent colorectal ESD at our hospital between July 2013 and December 2014 were studied. Cytological examination of intraluminal lavage samples associated incremental increases in lavage volume was collected. This prospective study was approved by the ethics committee of our hospital.

Results

No patients had exfoliated tumor cells in their samples before ESD. Four patients (20 %) had exfoliated tumor cells in their samples after lavage with 500 ml, while one patient (5 %) had exfoliated tumor cells after lavage with 1000 or 1500 ml.

Conclusion

Tumor cells are exfoliated into the intestinal lumen by tumor manipulation during colorectal ESD. There seems to be a risk for implantation after ESD, as well as rectal surgery. Sufficient intraluminal lavage of more than 1000 ml may be desirable to remove exfoliated tumor cells after colorectal ESD.

     

Clinical efficacy of naftopidil on lower urinary tract symptoms after radical prostatectomy

Objective:   The management of lower urinary tract symptoms that persist after radical prostatectomy remains to be established. We investigated whether an α1-blocker, naftopidil, improves LUTS in patients ≥1 year after radical prostatectomy.
Methods:   A total of 29 male patients received 25 mg/day of naftopidil for the first week, then 75 mg/day for 4 weeks. The frequency-volume chart, international prostate symptom score and quality of life index (QOL) were examined before and at the end of the 5-week administration in all subjects.
Results:   Total international prostate symptom score (I-PSS) and I-PSS subtotals associated with voiding symptoms and storage symptoms were significantly decreased at 5 weeks compared with baseline ( P  < 0.001 each). QOL index was significantly improved with naftopidil for 5 weeks ( P  < 0.001). From analyses of the frequency-volume chart, mean and maximum volume/void were significantly increased ( P  < 0.05 each).
Conclusion:   Lower urinary tract symptoms detected in patients ≥1 year after radical prostatectomy were markedly improved with administration of naftopidil at 75 mg/day. These symptoms could represent a novel target for medical treatment by improved understanding of the symptom pathology in the near future.     

Morphologic Features of Carotid Plaque Rupture Assessed by Optical Coherence Tomography

BACKGROUND AND PURPOSE:Rupture of the plaque fibrous cap and subsequent thrombosis are the major causes of stroke. This study evaluated morphologic features of plaque rupture in the carotid artery by using optical coherence tomography in vivo.MATERIALS AND METHODS:Thirty-six carotid plaques with high-grade stenosis were prospectively imaged by optical coherence tomography. “Plaque rupture” was defined as a plaque containing a cavity that had overlying residual fibrous caps. The fibrous cap thickness was measured at its thinnest part for both ruptured and nonruptured plaques. The distance between the minimum fibrous cap thickness site and the bifurcation point was also measured. Optical coherence tomography identified 24 ruptured and 12 nonruptured plaques.RESULTS:Multiple ruptures were observed in 9 (38%) patients: Six patients had 2 ruptures in the same plaque, 2 patients had 3 ruptures in the same plaque, and 1 patient had 5 ruptures in the same plaque. Most (84%) of the fibrous cap disruptions were identified at the plaque shoulder and near the bifurcation point (within a 4.2-mm distance). The median thinnest cap thickness was 80 μm (interquartile range, 70–100 μm), and 95% of ruptured plaques had fibrous caps of <130 μm. Receiver operating characteristic analysis revealed that a fibrous cap thickness of <130 μm was the critical threshold value for plaque rupture in the carotid artery.CONCLUSIONS:Plaque rupture was common in high-grade stenosis and was located at the shoulder of the carotid plaque close to the bifurcation. A cap thickness of <130 μm was the threshold for plaque rupture in the carotid artery.

Rupture of the fibrous cap and subsequent thrombosis are the major causes of cardiovascular events such as heart attack and stroke.^1–3 In a previous study of sudden coronary death, a fibrous cap thickness of 65 μm was chosen as a criterion of instability because for a cap to rupture, the average cap thickness was 23 ± 19 μm; 95% of caps measured <65 μm within a limit of only 2 SDs.¹ Therefore, the fibrous cap thickness of <65 μm is now widely accepted as the definition of in vivo coronary vulnerable plaque that is prone to rupture. Disruption of the fibrous cap is frequently observed in symptomatic carotid plaques^4,5 and is strongly associated with an ulceration appearance on angiography,⁶ which is considered an independent predictor of stroke on long-term follow-up in patients with symptomatic severe carotid stenosis.⁷ Redgrave et al⁸ examined the cross-sections of plaques with high-grade carotid stenosis and found that the optimum fibrous cap thickness for discriminating ruptured and nonruptured plaques was 200 μm; thus, it appears that there is no clear threshold for classifying plaques that are prone to rupture in vivo.Intravascular sonography, which is a widely used imaging method in the field of carotid artery intervention, has an axial resolution of 100–200 μm and a lateral resolution of 250 μm.⁹ Although it can visualize deep structures, intravascular sonography is not a suitable imaging technique for the detection of thin fibrous caps because its resolution is too low. Optical coherence tomography (OCT) has been introduced recently as a high-resolution imaging method.^10,11 The typical OCT image has an axial resolution of 10 μm, approximately 10 times higher than that of any other clinically available diagnostic imaging technique, such as intravascular sonography. OCT provides an accurate representation of the thickness of the fibrous cap that could not be measured by other imaging modalities.¹² In the present study, we evaluated the morphologic features of ruptured plaques in the carotid artery by using OCT.