Role of Sentinel Lymph Node Biopsy in the Staging of Synovial, Epithelioid, and Clear Cell Sarcomas

Background  Soft tissue sarcomas generally have a ≤5% risk of lymph node metastasis, but synovial, epithelioid, and clear cell subtypes reportedly have a much higher risk. The utility of sentinel lymph node biopsy (SLNB) for patients with these sarcoma subtypes is unknown. Methods  29 patients with nonmetastatic synovial, epithelioid, and clear cell sarcomas who underwent SLNB were examined. Results  Median age was 35 years (range 11–73 years), and 69% were male. Tumors were located in the lower extremity in 17 patients and the upper extremity in 12. The histological subtypes were synovial sarcoma in 16 patients, epithelioid sarcoma in 10, and clear cell sarcoma in 3. All patients had a staging chest computed tomography (CT) scan, none of which were suspicious, and 20 patients had staging positron emission tomography (PET) scans (16 negative, 3 indeterminate, and 1 suspicious). All patients had resection of their primary tumor. At least one sentinel node was found in 28 patients (97%), and the median number of sentinel nodes identified was 2 (range 1–4). One patient had a positive sentinel node on routine hematoxylin and eosin (H&E) staining and developed lung metastases. Two patients had positive sentinel nodes following immunohistochemical staining, and both remain disease free despite not undergoing completion lymphadenectomy. One patient developed a lymph node metastasis after a negative SLNB. Conclusion  For patients with these sarcoma subtypes without radiological evidence of nodal or distant metastases, the incidence of occult lymph node metastasis is relatively low. Determining utility of SLNB may require a multicenter trial.     

Psychological impact of types of sexual trauma among college women

Studies typically demonstrate that sexual victimization is associated with negative outcomes, yet they often fail to control for other trauma exposure and rarely address the impact of developmental level at the time of exposure or the type of sexual trauma experienced. The present study addresses these confounds by identifying groups of women with unique, nonoverlapping sexual trauma histories and examines the association between type of sexual trauma exposure and mental health impairment, social adjustment, and sexual functioning. This study compared five discrete groups of college-sophomore women based on self-identified trauma histories including no trauma, childhood sexual assault, childhood sexual abuse, adolescent sexual assault, and revictimization. Significant differences based on sexual trauma type were observed; individuals who experienced adolescent sexual assault or revictimization were at greatest risk for psychopathology, poor social adjustment, and risky sexual behaviors.     

Diagnostic implications of transcription factor Pax 2 protein and transmembrane enzyme complex carbonic anhydrase IX immunoreactivity in adult renal epithelial neoplasms

Pax 2, expressed by metanephric mesenchyme is vital for renal tubule formation and development. Carbonic anhydrase IX (CA IX) is implicated in cell proliferation, adhesion, and invasion. Data regarding expression in renal epithelial tumors other than clear cell renal cell carcinoma (RCC) are limited, conflicting, from tissue microarrays, and do not encompass the entire spectrum or novel uncommon variants. Conventional sections from 200 renal tumors comprising clear cell RCC (n=30), oncocytoma (n=17), papillary RCC (n=30), chromophobe RCC (n=50), urothelial carcinomas (n=30), collecting duct carcinomas (n=5), renal tumors with Xp11.2 translocation (n=15), tubulocystic carcinoma (n=19), and mucinous tubular spindle cell carcinoma (n=4) were immunostained for Pax 2 and CA IX. Clear cell RCC (28/30, 93%), oncocytoma (17/17, 100%), papillary RCC (16/30, 53%), and mucinous tubular spindle cell carcinoma (3/4, 75%) demonstrated nuclear immunoreactivity with Pax 2, whereas the other subtypes were nonreactive. Clear cell RCC (30/30, 100%), urothelial carcinoma (27/30, 90%), papillary RCC (17/30, 57%), and renal tumors with Xp11.2 translocation (6/15, 40%) exhibited membranous immunoreactivity with CA IX, whereas the other subtypes were nonreactive. This suggests potential diagnostic utility of Pax 2 in distinction of (i) oncocytoma (positive) from chromophobe RCC (negative), (ii) clear cell RCC and papillary RCC (positive) from renal tumors with Xp11.2 translocation (negative), and (iii) high-grade clear cell RCC (positive) from urothelial carcinoma (negative). CA IX expression has potential diagnostic implications including (i) clear cell RCC (positive) versus chromophobe RCC (negative) and (ii) urothelial carcinoma (positive) versus collecting duct carcinoma (negative). These antibodies may reliably discriminate between clinically significant subtypes of RCC with overlapping cytoarchitectural features.     

NOD/LtSz-Rag1nullPfpnull mice: a new model system with increased levels of human peripheral leukocyte and hematopoietic stem-cell engraftment

BACKGROUND: A critical need exists for effective small-animal models that accept engraftment of human hematopoietic progenitor cells and mature lymphocytes. The purpose of this study was to determine the phenotypic effects of perforin (Pfp) deficiency on nonobese diabetic (NOD)-Rag1null mice and to evaluate the ability of NOD/LtSz-Rag1nullPfpnull recipients to support engraftment with human hematolymphoid cells. METHODS: A new genetic stock of NOD mice doubly homozygous for targeted mutations at the recombination activating gene (Rag)-1 and Pfp genes was developed. NOD/LtSz-Rag1nullPfpnull mice were studied for immunopathologic and hematologic abnormalities. The ability of these mice to support engraftment with human peripheral blood mononuclear cells (PBMC) and umbilical-cord blood hematopoietic progenitor cells was assessed. RESULTS: NOD/LtSz-Rag1nullPfpnull mice lacked mature B cells, T cells, natural killer (NK) cell cytotoxic activity and were devoid of serum immunoglobulin (Ig) throughout a 37-week lifespan. These mice supported heightened engraftment with human PBMC as compared with NOD/LtSz-Rag1null controls as evidenced by a 4- to 5-fold increase in percentages of human lymphocytes and a 7- to 13-fold increase in percentages of CD4+ T cells in the peripheral blood and spleen. Total numbers of human CD4+ T cells were increased approximately 20-fold in the spleens of NOD/LtSz-Rag1nullPfpnull mice. These mice also showed approximately 12-fold higher levels of engraftment with human umbilical-cord blood cells compared with NOD/LtSz-Rag1null mice. CONCLUSIONS: NOD/LtSz-Rag1nullPfpnull mice are devoid of mature B cell, T cell, and NK cell cytotoxic activity, engraft at high levels with human PBMC, and hematopoietic progenitor cells and provide a new NK cell-deficient model for human hematolymphoid cell engraftment.     

Matched analysis of nonoperative management vs immediate appendectomy for perforated appendicitis

Background

The role of nonoperative therapy vs immediate appendectomy in the management of children with perforated appendicitis remains undefined. The objective of this study was to rigorously compare these management options in groups of patients with matched clinical characteristics.

Methods

Multicenter case-control study was conducted from 1998 to 2003. We compared patients treated nonoperatively vs those undergoing appendectomy to identify differences in 12 clinical parameters. We then generated a second control group of patients matched for these variables and compared the following outcomes in these clinically similar groups: complication rate, abscess rate, and length of stay (LOS). Analysis was performed according to intention-to-treat principles, using χ², Fisher exact, and Student t tests.

Results

The only significant difference between patients treated nonoperatively and those treated by appendectomy was the duration of pain on presentation (6.8 vs 3.1 days of pain).We created a second control group of patients undergoing immediate appendectomy matched on duration of pain on presentation to patients treated nonoperatively. These groups continued to be clinically comparable for the other 11 parameters. Compared to this matched control group, the nonoperative group had fewer complications (19% vs 43%, P < .01), fewer abscesses (4% vs 24%, P < .01), and a trend for shorter LOS (6.5 ± 5.7 vs 8.8 ± 6.7 days, P = .08).

Conclusions

When nonoperative management for perforated appendicitis was studied using appropriately matched clinical controls, we found that it resulted in a lower complication rate and shorter LOS in the subset of patients presenting with a long duration of pain. Our data suggest that nonoperative management should be prospectively evaluated in children with perforated appendicitis presenting with a history of pain exceeding 5 days.     

p16INK4A immunohistochemistry is superior to HPV in situ hybridization for the detection of high-risk HPV in atypical squamous metaplasia

In situ hybridization (ISH) assays for high-risk human papillomavirus (HR-HPV) and immunohistochemical (IHC) assays for surrogate markers such as p16 can be useful in detecting HR-HPV in cervical dysplasia, but the use of these markers in problematic cervical biopsies has not been well-established. We evaluated 3 chromogenic ISH assays (Ventana INFORM HPVII and HPVIII and DakoCytomation GenPoint) in conjunction with p16 IHC and HPV polymerase chain reaction in a study set consisting of 12 low-grade squamous intraepithelial lesions, 16 high-grade squamous intraepithelial lesions, and 30 benign cervix samples. A test set of 28 cases of atypical squamous metaplasia were also evaluated withVentana HPVIII ISH and p16 IHC. In the study set, the sensitivity of the DakoCytomation ISH assay (which detects HPV subtypes 16, 18, 31, 33, 35, 39, 45, 52, 56, 58, 59, and 68) was similar to the Ventana HPVII assay but less than that of the Ventana HPVIII ISH assay (both of which detect HPV subtypes 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, and 66) and less than p16 IHC (55.6% vs. 53.6 vs. 69.2% vs. 82.1%). All HPV ISH assays exhibited 100% specificity. p16 reactivity consisted of 2 patterns: focal strong and diffuse strong. Because focal strong p16 reactivity was identified in benign squamous epithelium (6.7% cases) and dysplastic epithelium, it was considered an equivocal result and only diffuse strong reactivity was considered to be specific for the presence of HR-HPV. In the squamous intraepithelial lesions study set, the difference in sensitivity between Ventana HPVIII ISH and p16 was not statistically significant. However, in the atypical squamous metaplasia test set cases, p16 reactivity (focal strong and diffuse strong) was significantly more sensitive than Ventana HPVIII ISH in correlating with the presence of human papillomavirus as detected by polymerase chain reaction (83.3% vs. 33.3% P=0.004). Because focal strong p16 reactivity is less specific, cases with this staining pattern are considered atypical and require further evaluation by other means. Overall, p16 IHC is considered the best candidate for the initial assessment of cervical biopsies that are histologically indeterminate for dysplasia given its wide availability, comparative ease of interpretation, and high sensitivity and specificity.     

Angiotensin-converting enzyme genotype and outcome in pediatric IgA nephropathy

Angiotensin-converting enzyme (ACE) I/D polymorphism has been implicated as a genetic marker for progression of glomerular disease. Studies of ACE genotypes in adults with IgA nephropathy (IgAN) have yielded conflicting results. We performed ACE genotyping on 79 patients with IgAN diagnosed prior to age 18 years who had either progressed to end-stage renal disease (ESRD) or are now more than 5 years post biopsy. Mean follow-up was 14.8 years for those with normal renal function. Forty-three (54.4%) subjects had normal renal function and a normal urinalysis at last evaluation. Sixteen (20%) progressed to ESRD and 1 has chronic renal insufficiency. Kaplan-Meier survival curves for progression to ESRD did not differ significantly for the ACE DD, ID, and II genotype groups (P=0.095, log-rank test). By univariate analysis, presence of hypertension and degree of proteinuria at diagnosis, and unfavorable histology but not ACE genotype, was significantly associated with progression to ESRD. In the Cox proportional hazards model that included grade of proteinuria, the ACE D allele was a significant independent predictor of outcome with a hazard ratio of 2.37 (P=0.031). Our data, while inconclusive, suggest that the ACE D allele may associate with poor outcome in pediatric IgAN.     

Assessment of family needs following acquired brain injury in Saskatchewan

Primary objective: The objective was to learn what the family members of individuals with acquired brain injury (ABI) perceived as important needs and to what extent these needs are being met.

Methods and procedures: Sixty-six individuals who care for someone with an ABI and who receive service from the Saskatchewan South ABI Outreach Team completed the Family Needs Questionnaire (FNQ).

Main outcomes: An analysis of the importance ratings found that the most important needs were related to health information. Most needs perceived as unmet were related to emotional support.

Conclusions: Caregivers indicated that having honest, accurate comprehensive information regarding the ABI survivor is important. Respondents also indicated that approximately one-half of the needs have gone unmet or only partly met. This study highlights the importance for service providers to assess family needs in order to minimize distress in caregivers, maintenance of the well being of whom is integral in the support of the person with ABI.     

Issues and challenges in staging of pressure ulcers.

Wound assessment is a key element of effective wound care, and assessment of pressure ulcers includes accurate determination of wound stage. Although the original staging system established by Shea was based on his understanding of the pathology involved in pressure ulcer development, subsequent staging systems (and the one currently in use) were intended simply to establish the level of tissue damage. Recently, clinicians have drawn attention to numerous limitations associated with the current staging system, including the inability to differentiate between an inflammatory response involving intact skin and a deep tissue injury (deep bruising) underneath intact skin. This is a clinically significant difference because clinicians have noted that most inflammatory responses resolve with intervention, whereas most areas of deep tissue injury progress to full-thickness ulcers even when appropriate intervention is provided. A second area of controversy involves partial-thickness (Stage 2) lesions; because many of these lesions are caused by maceration and/or friction (as opposed to pressure) clinicians are frequently unclear regarding which of these lesions should be staged. In response to these concerns, the National Pressure Ulcer Advisory Panel convened a consensus forum and published white papers to clearly outline the issues; they solicited clinician feedback on the white papers and the Wound, Ostomy, Continence Nurses Society provided a written response. This article summarizes the key points of the white papers, WOCN Society response, and consensus forum discussion.     

The blossoming of evidence-based clinical rheumatology: The Arthritis Research Campaign's Clinical Trials Collaboration in association with the MRC Clinical Trials Unit,BSR and BOA

Competing demands for scarce healthcare resources have accentuatedthe requirement for routine clinical practice to be evidence-based.One of the benchmarks for evidence-based medicine is the appropriatelyconducted randomized controlled trial (RCT). Although epidemiologicalstudies, whether case–control or cohort in design, havecontributed enormously to the generation of hypotheses and permitthe controlled evaluation of therapeutic interventions, theyare susceptible to biases through selection, information ascertainmentand confounding. While RCTs are also susceptible to such biases,the process of randomization and of blinded evaluation of outcomespermits the closest approximation in clinical research to theconduct of a hypothesis-testing laboratory experiment. Historically,there have been several obstacles to the execution of high-qualityRCTs to address important rheumatological questions. One