Prospective evaluation of prostate cancer detection by prostate specific antigen related parameters: comparison in serum and plasma samples.

PURPOSE: We compared the usefulness of serum and plasma samples for enhancing the specificity of prostate cancer detection. MATERIALS AND METHODS: We analyzed receiver operating characteristics curves to evaluate prospectively the cancer detection performance of prostate specific antigen (PSA) related parameters derived from serum and plasma samples in 248 and 249 consecutive patients, respectively. RESULTS: Receiver operating characteristics curve analysis showed that PSA density and transition zone PSA density were more powerful predictors of prostate cancer than total or free PSA in the group overall at intermediate serum PSA 2.1 to 10 ng./ml. and in the subgroup with total PSA 4.1 to 10 ng./ml. regardless of digital rectal examination findings. Percent free PSA performed significantly better than total PSA in patients with serum total PSA 4.1 to 10 ng./ml. PSA density, transition zone PSA density and percent free PSA did not differ substantially in patients with serum total PSA 4.1 to 10 ng./ml. However, none of these parameters distinguished patients with prostate cancer from those with benign histology when PSA was in the lower range of 2.1 to 4 ng./ml. The performance of these parameters was worse when plasma sample data were used for calculation. CONCLUSIONS: The performance of percent free PSA appears at least comparable to that of PSA density and transition zone PSA density in patients in this cohort with serum total PSA 4.1 to 10 ng./ml. without regard to digital rectal examination. The poor performance of these parameters in the lower PSA range underscores the need for other parameters to improve the specificity of cancer detection in elderly Japanese males. Continued use of serum samples is justified for measuring PSA related parameters by current assay techniques.     

Management of enterovesical fistula in patients with Crohn's disease

PURPOSE: Enterovesical fistula in patients with Crohn's disease is intractable. Although there are some reports that the enterovesical fistula were successfully treated conservatively, closure of the fistula cannot always be achieved and surgical intervention may required for those patients. Since surgical closure of entero-entero fistula has a high risk of relapse, the strategy for treating enterovesical fistula has not been established. We evaluated the clinical findings especially in management of enterovesical fistula in Crohn's disease. PATIENTS AND METHODS: Two hundred two patients (mean age was 28.4 year old, range 12-69; 152 men and 50 women) were diagnosed as Crohn's disease during a period of 15 years between 1986 and 2000 in our institute. The incidence and the clinical results regarding the diagnosis and the treatment of enterovesical fistula in these patients were retrospectively evaluated. RESULTS: Seven in 202 patients were diagnosed to have an enterovesical fistula (3.5%, 6 men and 1 woman). The period from the initial diagnosis of Crohn's disease to the recognition of the enterovesical fistula was 11 to 204 months (mean 92.1 months). Enterovesical fistula was revealed and/or visualized by radiological enterography in 6, cystography in 2, cystoscopy in 6, and CT in 4 patients. Surgical interventions were finally conducted in all 7 patients after the failure of conservative treatment for 10 to 146 days (mean 68.2 days). Surgical procedures performed for closing the enterovesical fistula were partial cystectomy with fistulectomy in 5, fistulectomy with bladder wall overlay-suture in 2, and bladder wall overlay-suture alone in 1. No relapse of enterovesical fistula was recognized in any patient in the average observation of 41.6 months. CONCLUSION: Although the treatment of Crohn's disease has been advanced, enterovesical fistula is shown to be resistant to conservative treatment options and it makes patients in unfavorable status for relatively long duration. Our evaluation shown here demonstrated the sufficient surgical results on the closure of enterovesical fistula without any relapse, and was different from the high relapse rate after the surgical management of entero-entero fistula in similar observation period. Surgical interventions of enterovesical fistula caused by Crohn's disease might have an advantage to make diseased patients improved in shorter duration.     

Role of cyclase activating parathyroid hormone (1-84 PTH) measurements during parathyroid surgery: potential improvement of intraoperative PTH assay

SUMMARY BACKGROUND DATA: Quick intraoperative parathyroid hormone assays are widely used as a guide to the adequacy of resection during parathyroid surgery. However, some authors have reported a 15% error rate of these assays because of the presence of false-positive and false-negative results. Recently the authors have found that most commercial intact PTH (iPTH) assays cross-react with non-(1-84) PTH (likely 7-84 PTH) and that the proportional levels of non-(1-84) PTH in patients were variable in a much wider range, accounting mostly for 20% to 60% of the immunoreactivity in samples obtained from hyperparathyroid patients. A cyclase activating PTH (CAP) measured by a novel immunoradiometric assay was shown to measure specifically 1-84 PTH. Using a CAP assay, the authors studied the rate of decline of CAP after parathyroidectomy and compared it with iPTH as measured by the Nichols intact PTH immunoradiometric assay. METHODS: This study comprised 29 patients with primary hyperparathyroidism (pHPT) caused by a single adenoma and 7 patients with secondary hyperparathyroidism (secondary HPT) who underwent parathyroidectomy. Blood samples were drawn after anesthesia, before excision of one enlarged parathyroid gland in pHPT and of the last gland in secondary HPT, and at 5, 10, and 15 minutes after excision. The 7-84 PTH level was calculated by subtracting the CAP value from the iPTH value. RESULTS: The percentage of 7-84 PTH in iPTH in plasma samples was 27.5 +/- 14.4% in pHPT and 39.6 +/- 15.1% in secondary HPT. In pHPT patients the plasma CAP and iPTH value decreased to 23.4 +/- 10.8 and 32.0 +/- 11.3% of the preexcision level at 5 minutes, 10.6 +/- 7.7 and 21.1 +/- 8.8% at 10 minutes, and 8.5 +/- 4.9 and 16.1 +/- 6.8% at 15 minutes after removal of the enlarged gland, respectively. At 5 minutes, CAP levels of all 29 pHPT patients had decreased to less than 40% of the preparathyroidectomy level; however, 7 (24%) patients still had an iPTH level of more than 40%. In secondary HPT patients, CAP and iPTH values had dropped to 43.3 +/- 20.2 and 66.1 +/- 19.7% at 5 minutes, 28.6 +/- 16.6 and 53.6 +/- 18.1% at 10 minutes, and 14.2 +/- 9.0 and 41.0 +/- 12.9% at 15 minutes after removal of the last enlarged gland, respectively. At 10 minutes, CAP levels of all seven secondary HPT patients had decreased to less than 50% of the preexcision level; however, three (43%) patients still had an iPTH level of more than 50%. In pHPT and secondary HPT, the 7-84 PTH level had dropped to 57.4 +/- 85.9 and 62.1 +/- 84.9%, respectively, of the preexcision value 15 minutes after removal of the enlarged gland or glands. CONCLUSIONS: The percentage of 7-84 PTH in iPTH in plasma samples varies substantially between patients with HPT. In both pHPT and secondary HPT, the plasma CAP value decreased more rapidly than iPTH after parathyroidectomy, depending on the amount of 7-84 PTH in circulation. These results suggest that the CAP assay may be a more useful adjunct to parathyroidectomy than the currently used iPTH assay.     

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.     

Erythropoietin protects the kidneys against ischemia reperfusion injury by activating hypoxia inducible factor-1alpha

BACKGROUND: Ischemia/reperfusion (I/R) injury is closely associated with tissue damage in various organs, as well as in kidney transplants. Erythropoietin (EPO) has been shown to have a cytoprotective effect against hypoxia. We examined the effect of EPO against renal I/R injury and the underlying mechanism. METHODS: Human umbilical vein endothelial cells and human renal proximal tubular epithelial cells were cultured under hypoxic conditions with various EPO concentrations at 37 degrees C and examined the mechanism of cell proliferation by EPO. Moreover, to demonstrate the renoprotective effect in vivo, we treated Sprague-Dawley rats with 100 IU/kg EPO every 2 days for 2 weeks (a total of 6 doses). One day after the last injection, the operations to produce renal I/R injury (bilateral renal occlusion for 60 min) were done, and rats were killed at the end of the reperfusion period (24 hr and 72 hr after reperfusion began). RESULTS: First, we demonstrated in vitro that EPO increased hypoxia inducible factor-1alpha (HIF-1alpha) expression and stimulated proliferation of both cells under hypoxic conditions. Next, we demonstrated in vivo that EPO treatment increased the number of HIF-1alpha-positive cells, and markedly induced the expression of vascular endothelial growth factor messenger RNA. Using pimonidazole, a molecular probe that detects hypoxia, we found that EPO markedly attenuated tubular hypoxia, and reduced the number of terminal transferase dUTP nick end labeling-positive apoptotic cells and alpha-smooth muscle actin-positive interstitial cells. CONCLUSIONS: We suggested a novel HIF-1alpha induction pathway by EPO under hypoxic conditions. Thus, EPO may protect the kidneys against ischemia reperfusion injury by activating HIF-1alpha.     

Brachiocephalic Vein Thrombus of Papillary Thyroid Cancer: Report of a Case

Differentiated thyroid cancer sometimes shows microscopic vascular invasion but rarely causes a tumor thrombus in a great vein. A preoperative diagnosis of the latter condition is difficult if a patient does not have any overt symptoms, but it is important for operative planning. We encountered a 26-year-old woman with papillary thyroid cancer and a tumor thrombus extending from the brachiocephalic vein to the superior vena cava. The tumor was successfully treated by surgical resection. To our knowledge only 19 such cases have so far been reported. We herein report our case, review the literature, and discuss the associated diagnostic problems and treatments including such areas as age, gender, symptoms, pathology, extension, and outcome. Received: October 20, 2000 / Accepted: July 17, 2001     

Repeated General Anesthesia in a Patient With Noonan Syndrome

Noonan syndrome (NS) is an autosomal dominant disorder characterized by facial anomalies, short stature, chest deformity, congenital heart diseases, and other comorbidities. The challenges faced during anesthetic management of patients with NS could be due to congenital heart diseases, hemostatic disorders, and airway anomalies. Here we describe dental treatment under general anesthesia performed for a 28-year-old man with NS. He had characteristic features of NS along with mild pulmonary valve stenosis. Dental treatment under general anesthesia was performed successfully on 13 occasions with nasotracheal intubation under curve-tipped suction catheter guidance or insertion of a reinforced laryngeal mask airway. This case suggests that for patients with NS, who might present several challenges, dental anesthesiologists should consider the extent of the patient''s disorders to enable them to perform dental treatment safely under general anesthesia.Key Words: Repeated general anesthesia, Noonan syndromeNoonan syndrome (NS) is an autosomal dominant disorder and was first reported by Noonan and Ehmke.¹ The primary features of this multisystem disorder include hypertelorism, low-set ears, down-slanting eyes, a webbed neck, congenital heart diseases, short stature, chest deformity, and intellectual impairment.^2,3 NS affects males and females equally and has an estimated incidence of 1 in 1000 to 1 in 2500 live births.^2,4The challenges faced during anesthetic management of patients with NS could be due to congenital heart diseases, hemostatic disorders, and airway anomalies.^5–8 The present report describes repeated administration of general anesthesia performed by adopting nasotracheal intubation or reinforced laryngeal mask airway insertion for a patient with NS at the time of dental treatment in our hospital.     

The effects of cyclosporin A and insulin on ischemic spinal cord injury in rabbits

We examined the effects of cyclosporin A (CsA), a drug that inhibits mitochondrial permeability transition pore, and insulin on ischemic spinal cord damage in rabbits. We assigned rabbits to 5 groups (n = 6 in each); sham barrier-opened group (sham BO), barrier-opened group (BO), barrier-opened-CsA group (BO-CsA), barrier-opened-insulin group (BO-I), and barrier-opened-CsA-insulin group (BO-CsA-I). The blood-spinal cord barrier was opened to facilitate drug penetration by a mild injury to the lumber spinal cord on day 1. CsA (10 mg/kg per day IV) was administered on day 3 to day 5 (total 30 mg/kg). Insulin was administered 30 min before ischemia. In all groups, spinal cord ischemia was produced on day 5 by occluding the abdominal aorta for 13 min. Neurological and histopathological evaluations were performed 4 days after ischemia. In group BO-CsA, blood glucose concentrations were significantly larger compared with the other four groups, and no protection was observed. In contrast, hindlimb motor function in groups BO-I and Bo-CsA-I and histopathology in group BO-CsA-I were significantly better than in groups sham BO, BO, and BO-CsA. The results indicate that insulin protects against ischemic spinal cord injury, whereas the effect of CsA is, at best, minimal.     

A neutralizing anti-fibroblast growth factor (FGF) 8 monoclonal antibody shows anti-tumor activity against FGF8b-expressing LNCaP xenografts in androgen-dependent and -independent conditions

BACKGROUNDS: Fibroblast growth factor 8-isoform b (FGF8b) has been detected in human clinical sex-organ related cancers including hormone-refractory prostate cancer. There are, however, few relevant experimental models. A murine monoclonal anti-FGF8 antibody, KM1334, has been shown to neutralize FGF8b and inhibit the growth of androgen-dependent mouse mammary SC-3 cells in vitro and in vivo. In the present study, we evaluated the anti-tumor activity of KM1334 against androgen-dependent and -independent progression of FGF8b-expressing human prostate cancer xenografts. METHODS: FGF8b cDNA was transfected into androgen-dependent human prostate cancer cell line LNCaP, and its xenograft tumors were established subcutaneously in SCID mice with or without castration. KM1334 at the dose of 400 microg/head was injected twice weekly. RESULTS: FGF8b-expressing LNCaP cells secreted FGF8b, showed enhanced level of Erk1/2 phosphorylation, and showed more potent growth properties than mock-expressing cells in vitro and in vivo. KM1334 reduced these properties in vitro, inhibited tumorigenecity in vivo (T/C=0.33), and showed anti-tumor activity against established tumors (T/C=0.47) of FGF8b-expressing cells. FGF8b-expressing LNCaP tumors were androgen-dependent. However, they recurred as androgen-independent FGF8b positive tumors after castration. KM1334 also inhibited the growth of established FGF8b-expressing tumors in the androgen-independent states (T/C=0.47). CONCLUSIONS: These results indicate that humanized monoclonal antibodies, conserving the paratope of KM1334, are a promising candidate for therapy of FGF8b-expressing clinical prostate cancers. Follow-up studies using xenograft models with clinical FGF8b-expressing tumors are required to validate these early findings.     

Spontaneous Rupture of the Pancreaticoduodenal Artery Possibly Related to Prior Occlusion of the Common Hepatic Artery: Report of a Case

We report herein a case of spontaneous rupture of the pancreaticoduodenal artery (PDA) associated with obstruction of the common hepatic artery. A 68-year-old man was admitted to our hospital following the sudden onset of severe upper abdominal pain. Computed tomography revealed a large mass formation in the peritoneal cavity. Hemorrhagic shock rapidly developed during the initial evaluation, necessitating an exploratory laparotomy to be performed in the emergency room. This revealed a large hematoma in the retroperitoneal space, and a ruptured PDA was sutured. Postoperative angiography showed obstruction of the common hepatic artery and also suggested that the source of the bleeding was the PDA. Thus, a diagnosis of spontaneous rupture of a PDA aneurysm associated with occlusion of the common hepatic artery was made. Following this case report, we discuss the development of true aneurysms of the PDA and the treatment of ruptured true PDA aneurysms resulting in shock. Received: September 18, 2000 / Accepted: July 17, 2001