Thrombotic Micro‐Angiopathy with Sirolimus‐Based Immunosuppression: Potentiation of Calcineurin‐Inhibitor‐Induced Endothelial Damage?

Thrombotic microangiopathy is a rare but important finding in the context of organ transplantation. Acute renal insufficiency in the setting of hemolysis and thrombocytopenia, a triad that constitutes 'hemolytic uremic syndrome', can be associated with, or triggered by, conditions such as verocytotoxin-producing Escherichia coli, viral infections, malignant hypertension, scleroderma, allograft rejection, lupus erythematosus, pregnancy, and medications including mitomycin C, calcineurin inhibitors, and oral contraceptives. After renal transplantation, it can occur, as either a de novo episode, or recurrent disease. Calcineurin inhibitors have long been associated with post-transplantation thrombotic microangiopathy. Sirolimus has been used as a primary immunosuppressant in patients transplanted with a history of earlier hemolytic-uremic syndrome, and also as rescue therapy in patients with calcineurin-inhibitor-associated thrombotic microangiopathy. We describe four cases where there was significant thrombotic microangiopathy in the context of contemporaneous or contiguous calcineurin inhibitor and sirolimus usage. As the intrarenal cyclosporin concentration is thought to be significantly elevated when cyclosporin and sirolimus are used together, this may explain these findings, and mandates caution in their co-administration.     

Cochlear implant benefits in deafness rehabilitation: PET study of temporal voice activations.

Cochlear implants may improve the medical and social prognosis of profound deafness. Nevertheless, some patients have experienced poor results without any clear explanations. One correlate may be an alteration in cortical voice processing. To test this hypothesis, we studied the activation of human temporal voice areas (TVA) using a well-standardized PET paradigm adapted from previous functional MRI (fMRI) studies. METHODS: A PET H(2)(15)O activation study was performed on 3 groups of adult volunteers: normal-hearing control subjects (n = 6) and cochlear-implanted postlingually deaf patients with >2 y of cochlear implant experience, with intelligibility scores in the "Lafon monosyllabic task" >80% (GOOD group; n = 6) or <20% (POOR group; n = 6). Relative cerebral blood flow was measured in 3 conditions: rest, passive listening to human voice, and nonvoice stimuli. RESULTS: Compared with silence, the activations induced by nonvoice stimuli were bilaterally located in the superior temporal regions in all groups. However these activations were significantly and similarly reduced in both cochlear implant groups, whereas control subjects showed supplementary activations. Compared with nonvoice, the voice stimuli induced bilateral activation of the TVA along the superior temporal sulcus (STS) in both the control and the GOOD groups. In contrast, these activations were not detected in the POOR group, which showed only left unilateral middle STS activation. CONCLUSION: These results suggest that PET is an adequate method to explore cochlear implant benefits and that this benefit could be linked to the activation of the TVA.     

Conspicuity of zones of ablation after radiofrequency ablation in porcine livers: comparison of an extracellular and an SPIO contrast agent

PURPOSE: To compare conspicuity of zones of ablation on nonenhanced, gadopentetate dimeglumine-(Gd-DTPA) and ferucarbotran-(SPIO)-enhanced magnetic resonance (MR) images. MATERIALS AND METHODS: In all, 33 radiofrequency ablations (RFA) were performed in 17 healthy porcine livers at 1.5T MR imaging 1 day and 2 and 4 weeks after RFA: T2-weighted (w) ultra turbo spin echo (UTSE), proton density (PD)-w UTSE, T1-w gradient echo (GRE) pre- and 5 minutes postcontrast administration, dynamic T1-w GRE during Gd-DTPA (Magnevist) or SPIO (Resovist) administration, T2-w UTSE, and PD-w UTSE sequences 10 minutes after SPIO administration. Regions of interest (ROIs) for contrast-to-noise ratio (CNR) and signal-to-noise ratio (SNR) were drawn in consensus by two radiologists. RESULTS: PD-w SPIO-enhanced images (23.5 +/- 5.5) showed higher liver-to-lesion CNR than T1-w GRE Gd-DTPA-enhanced images (13.5 +/- 6.1) 1 day after RFA (P < or = 0.05). At all other timepoints, liver-to-lesion CNR of PD-w and T2-w SPIO-enhanced images did not differ significantly from T1-w GRE Gd-DTPA-enhanced images (P > or = 0.05). Nonenhanced T2-w images revealed lower liver-to-lesion CNR (7.0 +/- 7.5/6.5 +/- 5.9/6.8 +/- 5.0, 1 day/2 weeks/4 weeks, respectively) than T2-w SPIO-enhanced (17.4 +/- 4.8/15.3 +/- 4.5/14.2 +/- 5.7), PD-w SPIO-enhanced (23.5 +/- 5.5/16.9 +/- 3.6, 1 day/2 weeks), and T1-w Gd-DTPA-enhanced (15.3 +/- 3.6/12.7 +/- 3.5, 2/4 weeks) images (P < or = 0.05). Liver-to-lesion CNR of SPIO-enhanced dynamic T1-w GRE images after 30, 80, 150, and 240 seconds did not change significantly over time (P > or = 0.05). CONCLUSION: One day after RFA lesion conspicuity on PD-w ferucarbotran-enhanced images is better than on T1-w GRE Gd-DTPA-enhanced images. At all other timepoints, ferucarbotran is not superior to gadolinium. Ferucarbotran- and gadolinium-enhanced images improve lesion conspicuity compared with nonenhanced T2-w images at all timepoints.     

Initial clinical results for breath-hold CT-based processing of respiratory-gated PET acquisitions

Purpose  Respiratory motion causes uptake in positron emission tomography (PET) images of chest structures to spread out and misregister with the CT images. This misregistration can alter the attenuation correction and thus the quantisation of PET images. In this paper, we present the first clinical results for a respiratory-gated PET (RG-PET) processing method based on a single breath-hold CT (BH-CT) acquisition, which seeks to improve diagnostic accuracy via better PET-to-CT co-registration. We refer to this method as “CT-based” RG-PET processing. Methods  Thirteen lesions were studied. Patients underwent a standard clinical PET protocol and then the CT-based protocol, which consists of a 10-min List Mode RG-PET acquisition, followed by a shallow end-expiration BH-CT. The respective performances of the CT-based and clinical PET methods were evaluated by comparing the distances between the lesions’ centroids on PET and CT images. SUV_MAX and volume variations were also investigated. Results  The CT-based method showed significantly lower (p = 0.027) centroid distances (mean change relative to the clinical method = −49%; range = −100% to 0%). This led to higher SUV_MAX (mean change = +33%; range = −4% to 69%). Lesion volumes were significantly lower (p = 0.022) in CT-based PET volumes (mean change = −39%: range = −74% to −1%) compared with clinical ones. Conclusions  A CT-based RG-PET processing method can be implemented in clinical practice with a small increase in radiation exposure. It improves PET-CT co-registration of lung lesions and should lead to more accurate attenuation correction and thus SUV measurement.     

Histological verification of 11C-choline-positron emission/computed tomography-positive lymph nodes in patients with biochemical failure after treatment for localized prostate cancer

OBJECTIVES

To evaluate the potential of ¹¹C‐choline‐positron emission tomography (PET)/computed tomography (CT) for planning surgery in patients with prostate cancer and prostate‐specific antigen (PSA) relapse after treatment with curative intent.

PATIENTS AND METHODS

We retrospectively reviewed the charts of 10 patients with PSA recurrence after either external beam radiation (two) or radical retropubic prostatectomy (eight) for prostate cancer, and who had a laparoscopic lymphadenectomy for suspicious lymph nodes detected on ¹¹C‐choline‐PET/CT. The histological results and PET/CT findings were compared.

RESULTS

In all, 22 suspicious lymph nodes were found on PET/CT, and 14 on conventional CT or magnetic resonance imaging. Comparing the conventional imaging showed concordance in 13 lymph nodes. Three of the 10 patients had no metastatic lymph node disease on definitive histology. The mean (sd ) PSA level for these patients was 1.0 (0.4) ng/mL, whereas that in patients with lymph node metastases was 15.1 (9.2) ng/mL (statistically significant difference, P < 0.05). The positive predictive value was seven of 10. All of the patients initially regressed, with PSA increases after lymphadenectomy. Two of the patients are being managed by watchful waiting, two had radiotherapy of the prostate fossa and two had chemotherapy with docetaxel. Four patients were treated by hormone‐deprivation therapy. After a mean (sd ) follow up of 11 (7) months, one patient died, one has PSA progression, but none of those with negative histology has clinical signs of local recurrence.

CONCLUSIONS

¹¹C‐choline‐PET is a valuable tool for detecting recurrent prostate cancer, but the limited positive predictive value should lead to a critical interpretation of the results.     

HIV prevention: What have we learned from community experiences in concentrated epidemics?

Drawing on lessons learned from community experiences in concentrated epidemics, this paper explores three imperatives in the effort to reduce the sexual transmission of HIV: combat prevention fatigue, diversify HIV testing and combat stigma and discrimination. The paper argues for a non‐judgmental harm reduction approach to the prevention of sexual transmission of HIV that takes into account the interpretation of risk by diverse individuals and communities in the era of antiretroviral therapy. This approach requires greater attention to increasing access to opportunities to know one's serostatus, especially among key populations at greater risk. Novel approaches to diversifying HIV testing approaches at community level are needed. Finally, the paper makes a plea for bold measures to combat stigma and discrimination, which continues to represent a formidable barrier for access to services for affected populations and may contribute to HIV‐related risk behaviours. A “triple therapy” approach to address stigma and discrimination is discussed, which includes greater acceptance of people living with HIV and AIDS (PLWHA), improving relevant laws and policies, and involving prevention users‐ working with people rather than for people‐. Note: this paper corresponds to the plenary talk of Bruno Spire at the XVIIth World AIDS Conference, August 8th, Mexico city: http://www.kaisernetwork.org/health_cast/player.cfm?id=4383     

Clinical utility of the PCA3 urine assay in European men scheduled for repeat biopsy

Background

The Prostate CAncer gene 3 (PCA3) assay has shown promise as an aid in prostate cancer (pCA) diagnosis in identifying men with a high probability of a positive (repeat) biopsy.

Objective

This study evaluated the clinical utility of the PROGENSA PCA3 assay.

Design, setting, and participants

This European prospective, multicentre study enrolled men with one or two negative biopsies scheduled for repeat biopsy.

Measurements

After digital rectal examination (DRE), first-catch urine was collected to measure PCA3 mRNA concentration and to calculate the PCA3 score. The PCA3 score was compared to biopsy outcome. The diagnostic accuracy of the PCA3 assay was compared to percent of free prostate-specific antigen (%fPSA).

Results and limitations

In 463 men, the positive repeat biopsy rate was 28%. The higher the PCA3 score, the greater the probability of a positive repeat biopsy. The PCA3 score (cut-off of 35) had a greater diagnostic accuracy than %fPSA (cut-off of 25%). The PCA3 score was independent of the number of previous biopsies, age, prostate volume, and total prostate-specific antigen (PSA) level. Moreover, the PCA3 score was significantly higher in men with high-grade prostate intraepithelial neoplasia (HGPIN) versus those without HGPIN, clinical stage T2 versus T1, Gleason score ≥7 versus <7, and “significant” versus “indolent” (clinical stage T1c, PSA density [PSAD] <0.15 ng/ml, Gleason score in biopsy ≤6, and percent positive cores ≤33%) pCA.

Conclusions

The probability of a positive repeat biopsy increases with rising PCA3 scores. The PCA3 score was superior to %fPSA for predicting repeat prostate biopsy outcome and may be indicative of clinical stage and significance of pCa.     

Main traumatic events in Europe: PTSD in the European study of the epidemiology of mental disorders survey

A potentially traumatic event (PTE) contributes to trauma through its frequency, conditional probability of posttraumatic stress disorder (PTSD), and experience of other PTEs. A cross-sectional survey was conducted, enrolling 21,425 adults nationally representative of six European countries. Using the WHO-Composite International Diagnostic Interview, 8,797 were interviewed on 28 PTEs and PTSD. Prevalence of 12-month PTSD was 1.1%. When PTSD was present, the mean number of PTEs experienced was 3.2. In a multivariate analysis on PTEs and gender, six PTEs were found to be more traumatic, and to explain a large percentage of PTSD, as estimated by their attributable risk of PTSD: rape, undisclosed private event, having a child with serious illness, beaten by partner, stalked, beaten by caregiver.     

Subareolar and peritumoral injection identify similar sentinel nodes for breast cancer

Background Sentinel lymph node (SLN) mapping with radioisotope and blue dye is rapidly becoming the standard of care for breast cancer. The optimal location for injection of radioisotope and blue dye is still being investigated. The goal of this study was to determine whether blue dye injection into the subareolar (SA) location localized the same sentinel nodes as the peritumoral (PT) location for patients with breast cancer. Methods Three hundred thirty-two patients with biopsy-proven operable breast cancer or ductal carcinoma in situ at two institutions underwent SLN mapping. Eighty-three patients had PT injection of blue dye (group 1), and 249 patients had SA injection of blue dye (group 2). All patients underwent PT injection of^99mTc-labeled sulfur colloid. Results The two groups were similar in age, previous biopsy type, and tumor size, location, and histology. The mean number of SLNs identified was 2.4 (range, 0–9) in group 1 and 2.5 (range, 0–11) in group 2. The SLN identification rate was 95% for group 1 and 97% for group 2. The isotope success rate was 94% for both groups. The blue dye success rate was 84% for group 1 and 90% for group 2. The isotope/blue dye concordance rate was 87% for group 1 and 90% for group 2. At a median follow-up of 28 months (range, 14 to 40), there were no axillary recurrences in any of the 332 patients. Conclusions These data suggest that delivery of mapping reagents in the SA and PT locations identifies similar lymph nodes. Because of simplicity and the similarity in node identification between SA and PT injection, further investigation of the SA site for delivery of SLN mapping reagents for breast cancer is warranted. Presented at the 54th Annual Cancer Symposium, Society of Surgical Oncology. Washington, DC, March 15–18, 2001.