Prediction of Gleason score upgrading in low-risk prostate cancers diagnosed via multi (≥12)-core prostate biopsy

Objectives  A paucity of data exists on actual pathology of the contemporary patients strictly categorized as having low-risk prostate cancer. We tried to identify useful preoperative predictors of Gleason score upgrading in patients who underwent radical retropubic prostatectomy (RRP) for low-risk prostate cancer diagnosed via multi-core prostate biopsy. Methods  A total of 203 patients who underwent radical RRP for low-risk prostate cancer, as defined by D’Amico et al.'s classification (clinical stage ≤T2a, biopsy Gleason sum ≤6, and PSA ≤10 ng/ml), detected via multi (≥12)-core prostate biopsy were enrolled. We reviewed patients preoperative and pathological data. Results  Among all subjects, 81 (39.9%) were upgraded to Gleason score ≥7 after RRP, whereas no downgrading was observed. In multivariate analysis, only preoperative PSA level (P = 0.024) and number of positive cores (P = 0.027) were observed to be independent predictors of Gleason score upgrading following RRP. Also, Gleason core upgrading was observed to be significantly associated with extraprostatic extension of tumor (P < 0.001) and positive surgical margin (P = 0.002). Conclusions  A significant proportion of patients with low-risk prostate cancer as defined by D’Amico et al.’s classification diagnosed via multi-core prostate biopsy in contemporary period may have Gleason score upgrading following RRP. For patients with low-risk prostate cancer, preoperative PSA level and number of positive cores may be useful predictors of Gleason score upgrading, which was observed to significantly associated with other adverse pathologic features.     

T2-Weighted Liver MRI Using the MultiVane Technique at 3T: Comparison with Conventional T2-Weighted MRI

Objective

To assess the value of applying MultiVane to liver T2-weighted imaging (T2WI) compared with conventional T2WIs with emphasis on detection of focal liver lesions.

Materials and Methods

Seventy-eight patients (43 men and 35 women) with 86 hepatic lesions and 20 pancreatico-biliary diseases underwent MRI including T2WIs acquired using breath-hold (BH), respiratory-triggered (RT), and MultiVane technique at 3T. Two reviewers evaluated each T2WI with respect to artefacts, organ sharpness, and conspicuity of intrahepatic vessels, hilar duct, and main lesion using five-point scales, and made pairwise comparisons between T2WI sequences for these categories. Diagnostic accuracy (Az) and sensitivity for hepatic lesion detection were evaluated using alternative free-response receiver operating characteristic analysis.

Results

MultiVane T2WI was significantly better than BH-T2WI or RT-T2WI for organ sharpness and conspicuity of intrahepatic vessels and main lesion in both separate reviews and pairwise comparisons (p < 0.001). With regard to motion artefacts, MultiVane T2WI or BH-T2WI was better than RT-T2WI (p < 0.001). Conspicuity of hilar duct was better with BH-T2WI than with MultiVane T2WI (p = 0.030) or RT-T2WI (p < 0.001). For detection of 86 hepatic lesions, sensitivity (mean, 97.7%) of MultiVane T2WI was significantly higher than that of BH-T2WI (mean, 89.5%) (p = 0.008) or RT-T2WI (mean, 84.9%) (p = 0.001).

Conclusion

Applying the MultiVane technique to T2WI of the liver is a promising approach to improving image quality that results in increased detection of focal liver lesions compared with conventional T2WI.     

Alveolar soft part sarcoma: MR and angiographic findings

Objective. To present the MR and angiographic findings of alveolar soft part sarcoma (ASPS). Design and patients. MR examinations (12 tumors of 10 patients) of ASPS performed at multiple hospitals were retrospectively reviewed. The tumors were found in the thigh (n=4), lower leg (n=4), femur (n=2, local metastasis), scalp (n=1) and arm (n=1). The MR signal characteristics including signal intensity, homogeneity and signal void of lesions and bony invasion including direct invasion or local metastasis were evaluated. Angiographic findings (n=4) and post-embolotherapy follow-up MR imaging (n=2) findings were also assessed. Results. Local bony metastasis was found in two cases. Seven tumors showed heterogeneous high signal intensity on T1- and T2-weighted images with good enhancement. One tumor had a very high signal on T1-weighted images. Eight tumors (67%) showed numerous signal voids in or near the tumors. All four angiographic studies showed numerous enlarged vessels, arteriovenous shunts and delayed washout. Two cases mimicked arteriovenous malformations on angiographic studies but MR images demonstrated solid soft tissue components as well as tortuous vessels. Conclusions. High signal on T1-weighted image and numerous signal voids are highly suggestive of ASPS, although they are not universal as has been suggested and arteriovenous malformation should be included in the differential diagnosis. Local bony metastases in ASPS were seen in two cases and should be carefully investigated. Received: 12 April 2000 Revision requested: 27 June 2000, 8 August 2000 Revision received: 2 August 2000, 21 August 2000 Accepted: 22 August 2000     

Pulmonary root translocation for repair of Taussig-Bing anomaly with interrupted arch

Anterior translocation of the pulmonary root was used as a new approach to the staged repair of Taussig-Bing anomaly with an interrupted aortic arch. It was performed to construct the right ventricle outflow tract with intraventricular baffling of the left ventricle to the aorta as the second stage operation after repair of the interrupted arch and pulmonary artery banding. This technique allows minimization of pulmonary regurgitation and has the major theoretical advantage for growth potential, which could diminish the need for reoperation.     

Antinociception of intrathecal adenosine receptor subtype agonists in rat formalin test

Adenosine has shown antinociceptive action via spinal adenosine receptors. There are four types of adenosine receptors: A1, A2A, A2B, and A3. We characterized the nature of types of adenosine receptors for the control of nociception at the spinal level. For nociception, formalin solution (5%, 50 microL) was injected into the hindpaw of male Sprague-Dawley rats. The effects of intrathecal adenosine A1 (CPA), A2A (DPMA), and A3 (IB-MECA) receptor agonists were examined. CPA and IB-MECA produced limited or no effect on the early phase response of the formalin test, respectively, but the two drugs depressed the late phase response. DPMA suppressed both phase responses. CPA was the most potent drug among the three in the late phase. These results suggest that spinal adenosine A1 and A2A receptors may be involved in the modulation of the early and the late phase responses of the formalin test, whereas adenosine A3 receptor may be involved in the regulation of the late phase response.     

Six-Month Prophylaxis Is Cost Effective in Transplant Patients at High Risk for Cytomegalovirus Infection

The risk of late-onset cytomegalovirus (CMV) infection remains a concern in seronegative kidney and/or pancreas transplant recipients of seropositive organs despite the use of antiviral prophylaxis. The optimal duration of prophylaxis is unknown. We studied the cost effectiveness of 6- versus 3-mo prophylaxis with valganciclovir. A total of 222 seronegative recipients of seropositive kidney and/or pancreas transplants received valganciclovir prophylaxis for either 3 or 6 mo during two consecutive time periods. We assessed the incidence of CMV infection and disease 12 mo after completion of prophylaxis and performed cost-effectiveness analyses. The overall incidence of CMV infection and disease was 26.7% and 24.4% in the 3-mo group and 20.9% and 12.1% in the 6-mo group, respectively. Six-month prophylaxis was associated with a statistically significant reduction in risk for CMV disease (HR, 0.35; 95% CI, 0.17 to 0.72), but not infection (HR, 0.65; 95% CI, 0.37 to 1.14). Cost-effectiveness analyses showed that 6-mo prophylaxis combined with a one-time viremia determination at the end of the prophylaxis period incurred an incremental cost of $34,362 and $16,215 per case of infection and disease avoided, respectively, and $8,304 per one quality adjusted life-year gained. Sensitivity analyses supported the cost effectiveness of 6-mo prophylaxis over a wide range of valganciclovir and hospital costs, as well as variation in the incidence of CMV disease. In summary, 6-mo prophylaxis with valganciclovir combined with a one-time determination of viremia is cost effective in reducing CMV infection and disease in seronegative recipients of seropositive kidney and/or pancreas transplants.Cytomegalovirus (CMV) infection remains one of most common opportunistic infections in solid organ transplant patients despite availability of specific and efficacious anti-viral drugs.^1,2 Solid organ transplant patients who have a negative CMV serology and receive an organ from a positive CMV serologic donor (D+/R−) have the highest incidence of CMV disease with and without prophylaxis.^2–5 Although the risk for CMV disease persists for life, the majority of cases occur shortly after completion of prophylaxis, often within the first year after transplant.⁶ CMV disease causes significant morbidity, increases mortality, and is associated with inferior transplant outcomes, particularly in the case of kidney transplantation.^7–10 Furthermore, the presence of CMV disease is one of the most frequent infectious causes of hospitalization early after transplantation, increasing the total cost of kidney transplantation and reducing its overall effectiveness.^7,11–13Valganciclovir (VGCV) is an effective anti-CMV agent for prophylaxis and treatment of CMV disease that is widely used in transplantation.^2,14–16 Although the recommended dose for CMV prophylaxis is 900 mg daily adjusted for renal function, a recent study showed that VGCV at 450 mg daily provides similar drug exposure compared with oral ganciclovir (GCV) at 1000 mg three times daily in kidney transplant patients, a dose similarly effective for CMV prophylaxis.^2,17 In most studies, VGCV prophylaxis consisted of 100 d after transplant, after which time the risk of CMV infection and disease increased.^2,18,19 Extending the duration of VGCV prophylaxis beyond the early post-transplant period may abrogate this transient increase in the risk of infection and disease.^20,21 In this regard, the optimal duration of prophylaxis for CMV D+/R− patients has not been determined and is the subject of ongoing study.²² Cost, efficacy, and safety are important factors in determining the optimal duration of VGCV prophylaxis. Over the past two decades, various strategies have been used including pre-emptive versus universal prophylaxis and shorter versus longer period of prophylaxis.^20,21,23,24 Although several clinical studies comparing universal prophylaxis versus pre-emptive anti-viral therapy have found similar efficacy and cost in managing CMV infection across various combinations of donor and recipient CMV serologic status, two meta-analyses did find that the use of universal prophylaxis was associated with reduced risk for CMV disease and death.^23–26This study is based on a single center experience comparing two CMV prophylaxis strategies. We report here the clinical outcome and cost-effectiveness analyses of 6- versus 3-mo VGCV prophylaxis in CMV D+/R− de novo kidney and/or pancreas transplant patients.     

Cyclosporin A therapy for severe Henoch-Schönlein nephritis with nephrotic syndrome

To evaluate the efficacy of cyclosporin A (CyA) for treating severe Henoch-Schönlein nephritis (HSN), seven patients with nephrotic syndrome, aged 3.9–13.8 years (mean 6.5 years), were analyzed retrospectively. Mean follow-up times were 5.5 years (range 2–9 years). All underwent renal biopsy before treatment, and follow-up renal biopsy was performed in six of the seven patients. All patients improved, with 24-h protein declining from a mean of 9.2 g/m²/day (range 1.5–16 g/m²/day) to 0.3 g/m²/day (range 0.03–1.2 g/m²/day) (p=0.016) and serum albumin increasing from a mean of 2.1 g/dl (range 1.5–2.4 g/dl) to 4.6 g/dl (range 3.5–5.3 g/dl) (p=0.016) after CyA therapy. The activity index decreased significantly at the second renal biopsies obtained at a mean interval of 11.7 months after the first (6.4±3.3 vs 3.5±1.2, p=0.042, respectively), while the chronicity index and the tubulointerstitial scores did not change. On the immunofluorescent findings at the second biopsies, the degree of deposits of immunoglobulins such as IgA, IgM, C3, and fibrinogen decreased in five of the six patients. Although this case series is without controls, our study suggests that CyA may be beneficial to a subset of HSN patients with nephrotic syndrome.     

Cyclosporine-induced renal injury induces toll-like receptor and maturation of dendritic cells

BACKGROUND: The toll-like receptor (TLR) is stimulated by not only pathogen-associated molecular patterns but also endogenous TLR ligands provided by injured cells. The influence of cyclosporine A (CsA)-induced renal injury on TLR expression and subsequent signaling pathway was evaluated. METHODS: Induction of chronic CsA nephropathy was made by administering CsA (15 mg/kg/day) for 28 days in rats. The TLR2 and TLR4 mRNA and protein expression, TLR-signaling pathway (MYD88, NF-kappaB and AP-1), putative TLR ligand (heat shock protein 70 [HSP70]), and maturation of dendritic cells were evaluated in CsA-treated rat kidneys. RESULTS: Long-term CsA treatment upregulated TLR2 and TLR4 mRNA and protein expression on renal tubular cells, and these were accompanied by increased MYD88, NF-kappaB and AP-1 expression. Putative TLR ligand (HSP70) was also significantly increased in CsA-treated rat kidney compared with vehicle-treated rat kidney. CsA-treatment increased expression of TNF-alpha mRNA, the number of dendritic cells, and expression of MHC class II antigen. Double-labeling of markers of dendritic cells and MHC class II antigen revealed that matured dendritic cells increased in CsA-treated rat kidney. CONCLUSIONS: CsA-induced renal injury stimulates components of innate immunity, and this finding suggests close association between CsA-induced renal injury and activation of innate immunity.     

Surgical outcomes of lateral approach for jugular foramen schwannoma: postoperative facial nerve and lower cranial nerve functions

The lateral surgical approach to jugular foramen schwannomas (JFS) may result in complications such as temporary facial nerve palsy (FNP) and hearing loss due to the complicated anatomical location. Ten patients with JFS surgically treated by variable methods of lateral approach were retrospectively reviewed with emphasis on surgical methods, postoperative FNP, and lower cranial nerve status. Gross total removal of the tumors was achieved in eight patients. Facial nerves were rerouted at the first genu (1G) in six patients and at the second genu in four patients. FNP of House–Brackmann (HB) grade III or worse developed immediately postoperatively in six patients regardless of the extent of rerouting. The FNP of HB grade III persisted for more than a year in one patient managed with rerouting at 1G. Among the lower cranial nerves, the vagus nerve was most frequently paralyzed preoperatively and lower cranial nerve palsies were newly developed in two patients. The methods of the surgical approach to JFS can be modified depending on the size and location of tumors to reduce injury of the facial nerve and loss of hearing. Careful manipulation and caution are also required for short facial nerve rerouting as well as for long rerouting to avoid immediately postoperative FNP.