bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract S4-5: Adjuvant Treatment with Zoledronic Acid in Stage II/III Breast Cancer. The AZURE Trial (BIG 01/04)
Authors: Coleman RE , Thorpe HC , Cameron D , Dodwell D , Burkinshaw R , Keane M , Gil M , Houston SJ , Grieve RJ , Barrett-Lee PJ , Ritchie D , Davies C , Bell R.
Published: April 2011

Background: The ABCSG XII trial demonstrated a 32% risk reduction in disease-free survival (DFS) events with Zoledronic acid (ZOL) use in a cohort of premenopausal women treated with endocrine therapy at 62 months median follow-up .[1,2] This strategy is increasingly being adopted in the wider breast cancer population. The AZURE trial is an academic study designed to determine whether treatment with ZOL added to standard adjuvant therapy improves DFS and bone metastasis-free survival (BMFS) in a broader range of patients with stage II/III breast cancer. Materials and methods: 3360 patients from 174 centres were randomized to receive (neo) adjuvant chemotherapy (CT) and/or endocrine therapy (ET) +/− ZOL 4mg iv every 3-4 weeks for 6 doses, then 3 monthly x 8 and 6 monthly x 5 to complete 5 years treatment. The primary DFS endpoint was to be determined after 940 DFS events, providing 80% power to detect a 17% reduction in hazard rates (HR) for DFS events. The rate of events on study has been slower than expected, resulting in an estimated final analysis in 2012. In light of the clinical interest in the results of AZURE, the DMEC has agreed to a second interim analysis after 705 events with boundaries set by an independent statistician, unaware of results at the first interim analysis, for both efficacy (HR ∼0.82, alpha spend 1%) and lack of clinical benefit (HR ∼0.935 with a 5% risk of declaring a false negative result). Contingent on DMEC advice, efficacy results that breach either boundary will be presented. A DMEC recommendation not to release the results at the second interim analysis may indicate that the point HR estimate lies between these boundaries.

Results: Patient characteristics including stage, number of positive axillary nodes, CT type, ER status, menopausal status and statin use were well balanced. 3208 patients (96%) received (neo) adjuvant CT (93% anthracyclines, 23% taxanes). 152 patients received ET alone. As of June 9th 2010, with a median follow up of 49 (IQR 42-56) months, there have been 695 DFS events. The safety population comprised 3340 patients (ZOL 1665; control 1675). The addition of ZOL to standard treatment did not significantly impact on chemotherapy delivery. Serious adverse events (SAE) were similar in both treatment arms. To date 13 confirmed (0.83%; 95% CI 0.38%, 1.28%) and 12 possible (1.12%; 95% CI 0.39%, 1.85%) cases of osteonecrosis of the jaw (ONJ) in the ZOL arm have occurred. Discussion: AZURE is one of the largest phase III studies of adjuvant bisphosphonates, and the results from this study will help define the role of adjuvant ZOL in the management of early breast cancer.

[1] Gnant M et al. NEJM 2009; 360(7):679-691

[2] Gnant M et al. ASCO 2010 Proceedings; abs #533.

Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr S4-5.
Abstract S4-6: Neoadjuvant Chemotherapy with or without Bevacizumab: Primary Efficacy Endpoint Analysis of the GEPARQUINTO Study (GBG 44)
Authors: von Minckwitz G , Eidtmann H , Rezai M , Fasching PA , Tesch H , Eggemann H , Schrader I , Kittel K , Hanusch C , Kreienberg R , Solbach C , Gerber B , Jackisch C , Kunz G , Blohmer J-U , Huober J , Hauschild M , Fehm T , Loibl S , Nekljudova V , Untch M.
Published: April 2011

Background: The anti-VEGF-receptor antibody bevacizumab (Bev) showed increased response rates and prolonged progression-free survival in combination with anthracyclines (A) and taxanes (T) in metastatic breast cancer (BC). One primary aim of the GeparQuinto phase III study was to improve pathological complete response (pCR) by adding Bev to AT-based neoadjuvant chemotherapy. We previously reported interim safety data showing more leukopenia, infections, mucositis, and hypertension, but less edema for the combination with Bev (von Minckwitz G et al, Ann Oncol 2010 in press).

Patients and Methods: Patients (P) with untreated HER2-negative BC were eligible if they had cT3/4a-d; or estrogen (ER) and progesterone (PgR) receptor-negative; or ER/PgR-positive tumors with clinically N+ (for cT2) or pNSLN+ (for cT1) disease, and no increased cardiac or bleeding risks. P were randomized to receive 4 cycles epirubicin/cyclophosphamide (EC) (90/600 mg/m2) q3w followed by 4 cycles docetaxel (D) (100mg/m2) with or without concomitant Bev 15mg/kg q3w added to chemotherapy cycles. P not clinically responding to EC ± Bev were considered as treatment failures and entered another part of the protocol. pCR was defined as no invasive or non-invasive tumor residuals in breast and nodes. We assumed a pCR rate of 14% (based on GeparDuo) and expected a pCR of 18.9% for EC-D+Bev (odds ratio 1.43). A two-sided Pearson's Chi2 with α=0.05 and β=0.20 calculated a sample size of 1934 P.

Results: Between 05/07 and 06/10 1889 P were randomized to EC-D (N=944) and EC-D+Bev (N=945). Median tumor size was 40/40 [-Bev/+Bev] mm (clinically) and 29/29 mm (sonographically); 6.3%/5.8% had T4a-c, 6.6%/6.7% T4d, 2.0%/2.1% bilateral, 14.3%/13.8% multifocal, and 8.8%/10.0% multicentric disease, 89.3%/88.9% had non-lobular, 42.5%/43.3% grade 3, 57.1%/58.4% node-positive, and 34.5%/33.6% ER and PgR-negative (triple-negative) disease. So far, 24% and 17% of patients did not respond to the first 4 cycles of EC-Bev and EC+Bev, respectively, and discontinued randomized treatment. The last randomized P will have surgery early Dec'10. Results on histological response and surgical outcome will be reported.

Conclusion: The GeparQuinto trial will provide for the first time randomized phase III efficacy data on Bev in combination to chemotherapy for patients with early breast cancer. pCR after Bev treatment can be considered as a surrogate marker for long term outcome but this has to be examined during further follow up of the patients.

Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr S4-6.
Abstract S4-7: Compliance with Mammographic Screening Guidelines from an Administrative Claims Database
Authors: Subar M , Lust SA , Lin W
Published: April 2011

BACKGROUND: Guidelines for breast cancer screening using mammography vary in terms of monitoring frequency and age at which screening should be performed. In November 2009, the US Preventive Services Task Force (USPSTF) modified their recommendations for women at average risk for breast cancer, now supporting first mammographic screening at age 50, with repeat mammograms every two years. The American Cancer Society and the Mayo Clinic continue to support yearly mammograms beginning at age 40. In two separate surveys performed after the USPSTF recommendations became public, 71% and 84% of women indicated an intention to undergo or continue mammographic testing during their 40's (Annals of Internal Medicine 2010; 152:531-532; USA Today 11/24/2009), but few studies have looked at actual screening frequency among women of different age groups. This study was performed to determine current pattern of testing as derived from an administrative medical claims database. METHOD: De-identified medical claims were reviewed from a 12-million member medical claims database at Medco Health Solutions, Inc. Claims for mammography for women 40 years of age and older eligible from January 2006 through December 2009 were reviewed. All women through age 64 had employer or health-plan based insurance coverage. Those 65 and older were covered through either an employer based retiree plan, or Medicare. Testing within each calendar year is reported. Annual testing was determined for women continuously eligible over the 4-year period. RESULTS: Among women 40-85 years old in any given year, 41-50% had a medical claim for a mammogram. Over the 4-year study (2006-2009), mean annual mammography rates were 41% (40-49 years old), 50.0% (50-64 years old), and 44% (65-85 years old). The percentage of women who were continuously eligible over the 4-year study period with any mammogram and with 1, 2, 3, or 4 or more mammograms over the 4-year study period are shown in the table below.

CONCLUSIONS: Although surveys indicate that over 70% of women support mammographic screening between ages 40-49, these data suggest that even among an insured population, many women do not have claims evidence of even one mammogram in 4 years and almost half of women do not receive biannual or more frequent mammography. These data also indicate that additional efforts are needed to reach the HealthyPeople 2010 goal of at least 70% of women aged 40 years or older having a mammogram in the past two years.

Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr S4-7.
Abstract S4-9: Comparing the Prediction of Chemotherapy Benefit in Patients with Node-Negative, ER-Positive Breast Cancer Using the Recurrence Score and a New Measure That Integrates Clinical and Pathologic Factors with the Recurrence Score
Authors: Tang G , Costantino JP , Crager M , Shak S , Wolmark N.
Published: April 2011

Background: The 21-gene Oncotype DX® Recurrence Score® (RS) is widely used for assessment of recurrence risk and prediction of chemotherapy benefit in patients with early stage ER-positive breast cancer. Through a meta-analysis on the NSABP B-14 study and the ATAC study, the Recurrence Score-Pathology-Clinical (RSPC) risk assessment has been developed as an integration of RS and clinico-pathologic factors (including tumor size, tumor grade and age) for assessment of recurrence risk in early stage ER-positive, node-negative breast cancer. The value of RSPC in prediction of chemotherapy benefit needs to be evaluated. Methods: In the NSABP trial B-20, patients were node-negative and ERpositive by the ligand binding assay, and were randomized to tamoxifen with or without adjuvant chemotherapy (MF or CMF). B-20 patients who had successful Oncotype DX RS assay and ER score ≥6.5 were included in this study. Cox proportional hazards models with interaction terms were used to evaluate RS and RSPC in prediction of chemotherapy benefit in reducing risk of distant recurrence.

Results: The analysis included 625 patients among whom 60 distant recurrence events occurred. RS showed a significant interaction with chemotherapy treatment (p=0.037), as found previously, with a standardized hazard ratio (HR) of 0.836. The interaction of RSPC with treatment was not significant (p=0.10), although the trend was in the same direction as RS (standardized HR 0.833).

Conclusions: RS used alone remains the best predictor of chemotherapy benefit in ER-positive, node-negative breast cancer.

Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr S4-9.
Abstract S5-1: Prospective Outcomes for Patients with Micro-Metastases and Macro-Metastases In Sentinel Nodes: NSABP B-32 Sentinel Node Trial
Authors: Julian TB , Anderson SJ , Golesorkhi N , Fourchotte V , Mamounas EP , Wolmark N.
Published: April 2011

Background: Sentinel node biopsy (SNB) allows for a more detailed analysis of axillary nodes, increasing the detection of nodal metastatic disease. Prospective outcome results related to patients with micro-and macro-metastases in sentinel nodes from the NSABP B-32 trial are presented here.

Methods: After stratification, women with operable invasive breast cancer and clinically negative nodes were randomly assigned to sentinel node resection (SNR) with immediate conventional axillary dissection (AD) [Group 1] or to SNR without AD [Group 2]. Group 2 patients with positive SNs underwent AD. Sentinel nodes underwent analysis by hematoxylin and eosin. Systemic therapy was at the discretion of the physician. Regional nodal irradiation for node positive lumpectomy patients and chest wall/regional node irradiation for node positive mastectomy patients was permitted. Univariate and multivariate analyses were carried out via Cox PH models to identify predictors of overall survival (OS) and disease-free survival (DFS).

Results: From May 1999 through February 2004, 5,611 patients were entered into NSABP B-32. A total 1,390 patients with positive SN were identified; 1,389 of these patients had follow-up data. There were 422 patients with macro-metastases (>2mm), 312 with micro-metastases (>0.2, ≥2.0mm), and 626 with unknown status. Median time in study was 94 months. 97% of SN-positive patients received systemic adjuvant therapy. Significant univariate predictors of OS and DFS were age, receptor status, clinical tumor size, histologic grade, number of positive SNs, SN metastasis size, number of positive nodes, lymphovascular invasion, and systemic therapy. Multivariate analysis identified histologic grade (HR: 2.30, P<0.0001), SN macrometastasis (HR: 2.44, p=0.0003), systemic therapy (HR: 0.22, P<0.0001), age, and clinical tumor size (CTS) as significant predictors of OS (Table 1) with similar predictors for DFS. For DFS, a significant quadratic effect due to age (p=0.015) was observed where younger and older women had higher risk of having an event than did middle aged women.

Conclusion: The most striking factors associated with poor OS and DFS were poor histologic tumor grade and macro-versus micro-SN metastases. Patients with micro-or macro-SN metastases who received systemic therapy had a 78% reduction in mortality and a 76% improvement of DFS.

Supported by: NCI U10-CA-69651, -12027, -37377, -69974.

Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr S5-1.
Abstract S5-5: Identification of a Clinically Relevant Gene Signature in Triple Negative and Basal-Like Breast Cancer
Authors: Rody A , Karn T , Liedtke C , Pusztai L , Ruckhäberle E , Hanker L , Gaetje R , Solbach C , Ahr A , Metzler D , Schmidt M , Müller V , Holtrich U , Kaufmann M.
Published: April 2011

Background: Gene expression profiles in breast cancer mainly reflect ER, PgR, HER2 status, and proliferation. Triple negative breast cancers (TNBC) seem to constitute a heterogenous entity and their relationship to basal-like breast cancers (BLBC) is not fully clear. Further understanding of TNBC is important since new treatments are needed.

Materials and Methods: We assembled an Affymetrix dataset of n=579 TNBC (finding cohort n=394, validation cohort n=185). Unsupervised methods identified principal metagenes differing among TNBC in this clean cohort. Clinical data were correlated to these metagenes for the basal-like and apocrine phenotypes, different types of immune cells, the claudin-CD24 signature, markers of blood and adipocytes, as well as signatures for stroma, angiogenesis, and inflammation.

Results: 73% of TNBC displayed a basal-like phenotype correlating with poor histological grading and younger age. However, no effect of basal-like phenotype on survival was observed. A good prognosis was obtained for expression of immune cell metagenes and a poor prognosis was associated with metagenes for inflammation, angiogenesis and stromal cells. A combination of high B-cell metagene and low IL-8 metagene expression identified 27% of TNBC with a favourable prognosis (HR 0.25, 95% CI 0.12-0.48; P<0.001) and remained the only significant factor in multivariate analysis with standard parameters.

Conclusion: All published prognostic signatures assign TNBC to a poor prognosis group. Use of a subtype-specific dataset not confounded by the main variables of breast cancer allowed the identification of a novel prognostic signature for TNBC. Targeting the IL-8 pathway could be a valuable therapeutic opportunity in TNBC.

Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr S5-5.
Abstract S6-3: Four vs 6 Cycles of Doxorubicin and Cyclophosphamide (AC) or Paclitaxel (T) as Adjuvant Therapy for Breast Cancer in Women with 0-3 Positive Axillary Nodes: CALGB 40101 — A 2x2 Factorial Phase III Trial: First Results Comparing 4 vs 6 Cycles of Therapy
Authors: Shulman LN , Cirrincione C , Berry DA , Becker HP , Perez E , O'Regan R , Martino S , Atkins JN , Hudis C , Winer E
Published: April 2011

Background: Four cycles of chemotherapy are frequently used as standard adjuvant chemotherapy for patients with low-risk primary breast cancer, though other regimens such as CAF, CMF, and TAC frequently are given for 6 cycles. Using a phase 3 factorial design we attempted to define whether 6 cycles of one chemotherapy regimen are superior to 4 cycles in patients with low-risk primary breast cancer. We also sought to determine if T would be equally efficacious as compared to AC, with reduced toxicity. Methods: The study enrolled women with operable breast cancer and 0-3 positive nodes. Study stratifiers were ER/PgR, HER2, and menopausal status. When the study was activated in May 2002, AC (60 and 600 mg/m2) was administered every 3 wks for 4 or 6 cycles, and T (80mg/m2) weekly for 12 or 18 wks. In 2003 (after 570 enrolled patients) treatment schedule was changed to every 2 wks for both AC and T (175 mg/m2), each given for 4 or 6 cycles. In 2008 accrual to the 6-cycle regimens was permanently closed due to slow accrual, with 3173 patients enrolled. The primary endpoint for this comparison was the superiority of 6 vs 4 cycles in relapse-free survival (RFS). The study was powered to have 567 RFS events. Data comparing AC with T are not yet available. Results: This report describes the impact of treatment duration and includes the 3173 patients randomized to 6- versus 4-cycles of chemotherapy, 93% of whom had node-negative disease. At a median follow-up of 4.6 years (2.5 - 8 yrs), the number of RFS events is 288 (with 138 on 4 cycles vs 150 on 6 cycles). The 4-yr RFS was 91.6% and 91.8% for 6 and 4 cycles, respectively. The Hazard Ratio of 6 to 4 cycles was 1.10 (95% CI = 0.87-1.39, p=0.42). Four-year OS was 95.3% and 96.4% for 6 and 4 cycles, respectively, with a HR of 6 to 4 cycles of 1.31 (95% CI = 0.95-1.82, p=0.097). Based on the present data the Bayesian predictive probability of concluding superiority of 6 cycles [a primary goal of the study] with 567 RFS events is only 0.001. There was no interaction between the number of cycles and type of chemotherapy, ER/PgR status, or HER2 status. In particular, the effect of number of cycles on RFS and OS was similar for both AC and T.

Conclusions: For women with primary breast cancer and 0-3 positive nodes, we found no evidence that extending chemotherapy from 4 to 6 cycles improves clinical outcome.

Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr S6-3.
Genomic Profiles Specific to Patient Ethnicity in Lung Adenocarcinoma
Authors: Broët Philippe , Dalmasso Cyril , Tan Eng Huat , Alifano Marco , Zhang Shenli , Wu Jeanie , Lee Ming Hui , Régnard Jean-François , Lim Darren , Koong Heng Nung , Agasthian Thirugnanam , Miller Lance D. , Lim Elaine , Camilleri-Broët Sophie , Tan Patrick
Published: April 2011

Purpose: East-Asian (EA) patients with non–small-cell lung cancer (NSCLC) are associated with a high proportion of nonsmoking women, epidermal growth factor receptor (EGFR)-activating somatic mutations, and clinical responses to tyrosine kinase inhibitors. We sought to identify novel molecular differences between NSCLCs from EA and Western European (WE) patients.

Experimental Design: A total of 226 lung adenocarcinoma samples from EA (n = 90) and WE (n = 136) patients were analyzed for copy number aberrations (CNA) by using a common high-resolution SNP (single nucleotide polymorphism) microarray platform. Univariate and multivariate analyses were carried out to identify CNAs specifically related to smoking history, EGFR mutation status, and ethnicity.

Results: The overall genomic profiles of adenocarcinomas from EA and WE patients were highly similar. Univariate analyses revealed several CNAs significantly associated with ethnicity, EGFR mutation, and smoking, but not to gender, and KRAS or p53 mutations. A multivariate model identified four ethnic-specific recurrent CNAs—significantly higher rates of copy number gain were observed on 16p13.13 and 16p13.11 in EA tumors, whereas higher rates of genomic loss on 19p13.3 and 19p13.11 were observed in tumors from WE patients. We identified several potential driver genes in these regions, showing a positive correlation between cis-localized copy number changes and transcriptomic changes.

Conclusion: 16p copy number gains (EA) and 19p losses (WE) are ethnic-specific chromosomal aberrations in lung adenocarcinoma. Patient ethnicity should be considered when evaluating future NSCLC therapies targeting genes located on these areas. Clin Cancer Res; 17(11); 3542–50. ©2011 AACR.
Pentostatin Plus Cyclophosphamide Safely and Effectively Prevents Immunotoxin Immunogenicity in Murine Hosts
Authors: Mossoba Miriam E. , Onda Masanori , Taylor Justin , Massey Paul R. , Treadwell Shirin , Sharon Elad , Hassan Raffit , Pastan Ira , Fowler Daniel H.
Published: April 2011

Purpose: The success of immunotoxin therapy of cancer is limited by host production of neutralizing antibodies, which are directed toward the Pseudomonas exotoxin A (PE) component. In this proof-of-principle study using a well-established murine model, we hypothesized that a newly developed immune depletion regimen consisting of pentostatin plus cyclophosphamide would abrogate anti-immunotoxin reactivity.

Experimental Design: BALB/c hosts were injected weekly with recombinant immunotoxin (RIT) SS1P, which is an antimesothelin Fv antibody fragment genetically fused to a 38 kDa portion of PE, and has been evaluated in clinical trials. Experimental cohorts received induction chemotherapy consisting of pentostatin (P) plus cyclophosphamide (C) prior to initial RIT exposure; some cohorts received further maintenance PC therapy of varying intensity just prior to each weekly RIT challenge. Cohorts were monitored for T, B, myeloid cell depletion, and for total anti-SS1P antibody (Ab) formation.

Results: Controls uniformly developed anti-SS1P Ab after the third RIT exposure. Induction PC therapy reduced the frequency of hosts with anti-SS1P Ab. Abrogation of antibody generation was improved by maintenance PC therapy: nearly 100% of recipients of intensive PC maintenance were free of anti-SS1P Ab after 9 weekly RIT doses. The most effective PC regimen yielded the greatest degree of host B-cell depletion, moderate T-cell depletion, and minimal myeloid cell depletion.

Conclusions: Induction and maintenance PC chemotherapy safely prevented anti-immunotoxin antibody formation with uniform efficacy. These data suggest that immunotoxin therapy might be used in combination with pentostatin plus cyclophosphamide chemotherapy to improve the targeted therapy of cancer. Clin Cancer Res; 17(11); 3697–705. ©2011 AACR.
Pharmacologic Inhibition of ALK5 Causes Selective Induction of Terminal Differentiation in Mouse Keratinocytes Expressing Oncogenic HRAS
Authors: Markell Lauren Mordasky , Masiuk Katelyn E. , Blazanin Nicholas , Glick Adam B.
Published: April 2011

TGFβ has both tumor suppressive and oncogenic roles in cancer development. We previously showed that SB431542 (SB), a small molecule inhibitor of the TGFβ type I receptor (ALK5) kinase, suppressed benign epidermal tumor formation but enhanced malignant conversion. Here, we show that SB treatment of primary K5rTA/tetORASV12G bitransgenic keratinocytes did not alter HRASV12G-induced keratinocyte hyperproliferation. However, continuous SB treatment significantly enhanced HRASV12G-induced cornified envelope formation and cell death linked to increased expression of enzymes transglutaminase (TGM) 1 and TGM3 and constituents of the cornified envelope small proline-rich protein (SPR) 1A and SPR2H. In contrast, TGFβ1 suppressed cornified envelope formation in HRASV12G keratinocytes. Similar results were obtained in HRASV12G transgenic mice treated topically with SB or by coexpressing TGFβ1 and HRASV12G in the epidermis. Despite significant cell death, SB-resistant HRASV12G keratinocytes repopulated the primary culture that had overcome HRas-induced senescence. These cells expressed reduced levels of p16ink4a and were growth stimulated by SB but remained sensitive to a calcium-induced growth arrest. Together these results suggest that differential responsiveness to cornification may represent a mechanism by which pharmacologic blockade of TGFβ signaling can inhibit the outgrowth of preneoplastic lesions but may cause a more progressed phenotype in a separate keratinocyte population. Mol Cancer Res; 9(6); 746–56. ©2011 AACR.
Triple Immunocytochemical Staining in Fine-Needle Aspirate of a Neck Mass: A Case Report and Review of the Literature
Authors: James Daniel T. , Taheri Touraj , Skerman Joanna
Published: April 2011

Background: Immunocytochemistry involving single or double antibodies can be used to support or confirm a diagnosis in difficult cytology cases. There are a few reports on the application of a cocktail of 3 antibodies in the literature. We would like to report our experience using this technique in a difficult case of cervical lymph node fine-needle aspiration cytology (FNAC). Case: A 75-year-old woman presented with a left neck mass for which FNAC was performed. The aspirates were cellular comprising atypical cells present in loose aggregates. The cells exhibited an ovoid and spindled morphology with no evidence of keratinization or any other differentiating features. The cytology was suggestive of metastatic poorly differentiated neoplasm; however, the presence of ovoid histiocytic-looking cells required further assessment. Triple immunostaining using a cocktail of CK5/6, CK34, and CD68 was performed. The spindled atypical cells were positive for CK5/6 and CK34 (brown cytoplasmic staining) and the ovoid histiocytic-looking cells were positive for CD68 (red cytoplasmic staining). Based on immunostaining, the cytological diagnosis of metastatic squamous cell carcinoma was confirmed. Conclusion: In view of our findings, the utility of triple immunocytochemical staining in cytology smears of poorly differentiated malignancy and a brief review of the literature are highlighted in this report.
Primary Amyloidosis Involving Mesenteric Lymph Nodes: Diagnosis by Fine-Needle Aspiration Cytology
Authors: Bhavsar Tapan , Vincent Gregory , Durra Heba , Khurana Jasvir S. , Huang Yajue
Published: April 2011

Background: Mesenteric lymph node amyloid deposits are rare and may be seen in isolated or secondary amyloidosis. The diagnosis of mesenteric amyloidosis has conventionally relied on histopathological examination following an exploratory laparotomy or a biopsy. Case: A 72-year-old male previously diagnosed with Waldenström’s macroglobulinemia and multiple other malignancies was admitted for abdominal pain. An abdominal computed tomography (CT) scan revealed diffuse retroperitoneal and mesenteric lymphadenopathy associated with bowel wall thickening. A CT-guided fine-needle aspiration (FNA) cytology and core biopsies of mesenteric lymph nodes were performed. The FNA smears revealed irregular, waxy, basophilic clumps on a Diff-Quik stain and cyanophilic clumps of amorphous material on a Papanicolaou stain. The lymph node aspirates showed positivity for the Congo red stain, confirming it as amyloid. In situ hybridization studies revealed a predominance of λ light chains, and a diagnosis of primary amyloidosis involving mesenteric lymph nodes was made. Supplemental needle core biopsies showed positivity for Congo red and Crystal violet stains and exhibited the classic apple-green birefringence under polarized light. Conclusion: The involvement of lymph nodes in amyloidosis is not uncommon; however, the involvement of mesenteric lymph nodes in a setting of macroglobulinemia and its diagnosis by FNA cytology is novel to this case.
Cytomorphology of Crystal Storing Histiocytosis in the Breast Associated with Lymphoma: A Case Report
Authors: Gao Faye F. , Khalbuss Walid E. , Austin R. Marshall , Monaco Sara E.
Published: April 2011

Crystal storing histiocytosis (CSH) is a very rare immunoglobulin (Ig) deposition disorder in which macrophages accumulate light chains or Ig crystalline inclusions. It is frequently associated with lymphoproliferative disorders, but can be seen in some reactive conditions too. This article reports the cytomorphologic, histopathologic, and ancillary study findings of a marginal zone B cell lymphoma of the breast with CSH in a 54-year-old woman. To the best of our knowledge, this is the first report describing CSH in the breast and one of a few reports describing the cytomorphology of CSH. In breast fine-needle aspiration biopsies, CSH can be confused with benign processes such as fat necrosis and histiocytic lesions. Thus, awareness of this rare entity and its frequent association with lymphoproliferative disorders is useful in order to triage a specimen appropriately and exclude the possibility of a lymphoproliferative process.
Preliminary Study of a New, Fully Automated System for Liquid-Based Cytology: The NovaPrep® Processor System
Authors: Esquivias López-Cuervo Javier , Montalbán Beltran Estanislao , Cuadros Lopez Jose Luis , Alonso Castillo Angeles , Nieto Sanchez Teresa
Published: April 2011

Objective: To evaluate a fully automated system for liquid-based cytology (LBC): the NovaPrep® Processor System (NPS), which is based on the new concept of double decantation, versus conventional cytology (CC), the gold standard for cytology. Study Design: We performed a preliminary comparative study involving 1,129 female patients who underwent sampling for a Pap test; the sample was first smeared for CC and then, using the remaining specimen on the brush, for LBC with the NPS. The performances of CC and NPS were evaluated for accuracy and compared using the gold standard of a combination of one of the two methods of pathological cytology with screening for positive human papilloma virus, quantification of cells (normal and pathological), and improvement in the quality of samples and reading time. Results: The results showed improvement in sensitivity (3.81% for CC vs. 4.52% for NPS) with a specificity superior to 90% for both, a markedly decreased number of unsatisfactory specimens, notably samples containing too many inflamed cells (7.4% for CC vs. 0.5% for NPS), and a shortening of the reading time, which was three times less using NPS. Conclusion: This preliminary study showed a gain in sensitivity, a drop in the number of unsatisfactory specimens and a reduction in reading time with NPS. The results achieved using this fully automated LBC procedure are very promising and will hopefully reduce the overall cost of cervical cancer screening in the future.
Carotid Intima-Media Thickness Is Increased Not Only in Non-Alcoholic Fatty Liver Disease Patients but Also in Alcoholic Fatty Liver Patients
Authors: Kim Jeong Han , Kim Seung Young , Jung Eun Seok , Jung Sung Woo , Koo Ja Seol , Kim Ji Hoon , Yeon Jong Eun , Kwon So Young , Lee Sang Woo , Byun Kwan Soo , Lee Chang Hong
Published: April 2011

Background/Aims: There are many reports of non-alcoholic fatty liver disease (NAFLD) patients with increased carotid intima-media thickness (IMT). However, there is little information about carotid IMT in alcoholic fatty liver disease (AFLD) patients. We aimed to compare the carotid IMT of NAFLD patients and AFLD patients. Methods: The medical records of individuals who underwent carotid IMT measurement and abdominal ultrasonography between January 2006 and December 2008 at Korea University Ansan Hospital were retrospectively reviewed. The patients were divided into group A (no fatty liver without alcohol history), group B (NAFLD), group C (AFLD) and group D (no fatty liver with alcohol history). The carotid IMT results were compared across all groups. Results: The mean carotid IMT was 0.55 ± 0.1 mm for group A, 0.6 ± 0.1 mm for group B, 0.59 ± 0.1 mm for group C, and 0.54 ± 0.1 mm for group D. There were significant differences between groups A and B, groups A and C, and groups C and D (p < 0.05), but there were no differences between groups B and C (p = 0.736). Conclusions: We determined that patients with fatty livers have an increased carotid IMT both in NAFLD and AFLD patients.
Survival Outcome Associated with the Screening Interval for Gastric Cancer in Korea
Authors: Lee Hyuk , Min Byung-Hoon , Lee Jun Haeng , Son Hee Jung , Kim Jae J. , Rhee Jong Chul , Kim Seonwoo , Rhee Poong-Lyul
Published: April 2011

Background/Aims: Early gastric cancer (EGC) can be treated by endoscopic resection, which results in an excellent prognosis. Optimal screening intervals considering risk factors for gastric cancer have not been established. The aim of this study was to determine the maximum gastric cancer screening interval in terms of long-term survival. Methods: Curative resection was performed in 561 patients with gastric cancer who had completed a questionnaire on their previous history of screening tests and risk factors. The association between EGC detection rate and previous screening history was evaluated, and 5-year disease-free survival rates were compared between various screening intervals. Results: Multivariate analysis showed that intestinal metaplasia [hazard ratio (HR) 9.690, 95% confidence interval (CI) 5.896–15.927] and previous screening history (HR 0.077, 95% CI 0.048–0.125) were independent factors associated with advanced gastric cancer. In patients without intestinal metaplasia, there was no significant difference in the extent of gastric cancer progression and the 5-year disease-free survival rate between groups with screening intervals of less than 3 years. In patients with intestinal metaplasia, the cutoff screening interval for detection of EGC and disease-free survival was 2 years. Conclusion: The optimum screening interval for disease-free survival for gastric cancer in a normal population is 3 years, but a screening interval of 2 years should be used for patients with intestinal metaplasia in Korea.
The Role of Sediment Cytology in Ovarian Neoplasm
Authors: Shahid Mohammad , Siddiqui Farhan Asif , Mubeen Aysha , Shah Surbhi , Sherwani Rana K.
Published: April 2011

Objective: It was our aim to study the role of sediment cytology in a diagnostic evaluation of ovarian neoplasm. Methods: The present study was conducted in the Department of Pathology, Jawaharlal Nehru Medical College, AMU, Aligarh, India, over a span of 22 months. Cytological smears were prepared by centrifuging the sediment of fluid from the bottom of a container in which surgical specimens were received. Smears were fixed in 95% ethyl alcohol and then stained using hematoxylin-eosin and Papanicolaou stains. The cytological results were compared with histological diagnosis, taking the latter as gold standard. Results: Out of 54 lesions studied by sediment cytology, 22 lesions were labeled as benign, 26 lesions as malignant and 6 lesions were inconclusive. Final histological diagnoses labeled 24 lesions as benign and 30 lesions as malignant. Comparing the diagnosis of the cytology smear with the histological section, 44 out of 54 cases were concordant. A sensitivity, specificity and diagnostic accuracy of 90.3, 92.3 and 90.3% was achieved, respectively. Conclusion: Biopsy sediment cytology is a good complementary method to histopathology in the study of ovarian biopsy material. In developing countries like ours, where the facility of frozen section is not available at many centers, this simple and cheap technique can be of much help in rapid diagnosis.
The Effect of Chlorhexidine Varnish on Root Caries: A Systematic Review
Authors: Slot D.E. , Vaandrager N.C. , Van Loveren C. , Van Palenstein Helderman W.H. , Van der Weijden G.A.
Published: April 2011

Objective: The aim of this study was to systematically review the present literature on the effect of chlorhexidine varnish (CHX-V) on root caries. Materials and Methods: The MEDLINE-PubMed, the Cochrane-CENTRAL and EMBASE databases were searched through December 2010 to identify any appropriate studies. Root caries incidence and root caries activity were selected as outcome variables. Results: An independent screening of the unique titles and abstracts of 24 MEDLINE-PubMed, 14 Cochrane-CENTRAL and 18 EMBASE papers resulted in 6 publications that met the eligibility criteria. Data extraction provided no conclusive evidence that the application of CHX-V is effective in patients when regular professional oral prophylaxis is performed. If effective, the 40% CHX-V was found to provide a benefit over a control or fluoride varnish. CHX-V at lower concentrations (1 and 10%) may provide protection against root caries in high-risk patients (such as geriatric and xerostomia patients) in the absence of regular professional oral prophylaxis. Conclusion: Within the limitations of this review, it may be concluded that in the absence of regular professional tooth cleaning and oral hygiene instructions, CHX-V may provide a beneficial effect in patients in need of special care. The strength of this recommendation is graded as ‘weak’.
Midlife Healthy-Diet Index and Late-Life Dementia and Alzheimer’s Disease
Authors: Eskelinen Marjo H. , Ngandu Tiia , Tuomilehto Jaakko , Soininen Hilkka , Kivipelto Miia
Published: April 2011

Aim: To study long-term effects of dietary patterns on dementia and Alzheimer’s disease (AD). Methods: Of 525 subjects randomly selected from population-based cohorts surveyed at midlife, a total of 385 (73%) subjects were re-examined 14 years later in the CAIDE study. A healthy-diet index (range 0–17) was constructed including both healthy and unhealthy dietary components. Results: Persons with a healthy diet (healthy-diet index >8 points) had a decreased risk of dementia (OR 0.12, 95% CI 0.02–0.85) and AD (OR 0.08, 95% CI 0.01–0.89) compared with persons with an unhealthy diet (0–8 points), adjusting for several possible confounders. Conclusions: Healthy diet at midlife is associated with a decreased risk of dementia/AD in late life. These findings highlight the importance of dietary patterns and may make more effective measures for dementia/AD prevention or postponement possible.
Amnestic Mild Cognitive Impairment and Early Alzheimer’s Disease in an Asian Memory Clinic – Evidence for a Clinical Spectrum
Authors: Chan M. , Tay L. , Chong M.S.
Published: April 2011

Objectives: To determine if mild cognitive impairment (MCI) represents a continuum of cognitive and functional deficits. Methods: Clinical data of 164 subjects with no dementia (ND, n = 52), uncertain dementia (n = 69), and mild probable Alzheimer’s disease (AD, n = 43) were reviewed. Uncertain dementia patients were classified as pre-MCI (n = 11), early amnestic MCI (e-aMCI, n = 15) and late amnestic MCI (l-aMCI, n = 15). Cognitive assessments [Chinese Mini-Mental State Examination (CMMSE) and a validated neuropsychological battery], functional assessments (Lawton’s scale for instrumental activities of daily living) and neuroimaging (ischemic lesions and medial temporal lobe atrophy) were reviewed. Results: ND, aMCI and mild AD subjects demonstrated a significant trend for worsening performance for all cognitive and functional measures (ANOVA, p < 0.05). Pre-MCI subjects performed significantly better than aMCI subjects in all verbal memory domains (p < 0.001), while l-aMCI had worse functional performance (p = 0.007), a trend towards greater depressive symptoms (p = 0.05) and higher medial temporal lobe atrophy scores (p = 0.06). l-aMCI subjects were more likely than either pre-MCI or e-aMCI to progress to dementia over a mean follow-up period of 2.5 years (46.7 vs. 9.1 and 20.0%, respectively). Conclusions: Clinical delineation of aMCI allows the differentiation of those likely to progress for better correlation to biomarker development.
Metabolic Syndrome, Components, and Cardiovascular Disease Prevalence in Chronic Kidney Disease: Findings from the Chronic Renal Insufficiency Cohort (CRIC) Study
Authors: Townsend Raymond R. , Anderson Amanda H. , Chen Jing , Gadebegku Crystal A. , Feldman Harold I. , Fink Jeffrey C. , Go Alan S. , Joffe Marshall , Nessel Lisa A. , Ojo Akinlolu , Rader Daniel J. , Reilly Muredach P. , Teal Valerie , Teff Karen , Wright Jackson T. , Xie Dawei ,   for the CRIC Study Investigators
Published: April 2011

Background/Aims: Metabolic syndrome may increase the risk for incident cardiovascular disease (CVD) and all-cause mortality in the general population. It is unclear whether, and to what degree, metabolic syndrome is associated with CVD in chronic kidney disease (CKD). We determined metabolic syndrome prevalence among individuals with a broad spectrum of kidney dysfunction, examining the role of the individual elements of metabolic syndrome and their relationship to prevalent CVD. Methods: We evaluated four models to compare metabolic syndrome or its components to predict prevalent CVD using prevalence ratios in the Chronic Renal Insufficiency Cohort (CRIC) Study. Results: Among 3,939 CKD participants, the prevalence of metabolic syndrome was 65% and there was a significant association with prevalent CVD. Metabolic syndrome was more common in diabetics (87.5%) compared with non-diabetics (44.3%). Hypertension was the most prevalent component, and increased triglycerides the least prevalent. Using the bayesian information criterion, we found that the factors defining metabolic syndrome, considered as a single interval-scaled variable, was the best of four models of metabolic syndrome, both for CKD participants overall and for diabetics and non-diabetics separately. Conclusion: The predictive value of this model for future CVD outcomes will subsequently be validated in longitudinal analyses.
Balloon Angioplasty and Stenting of Branch Pulmonary Arteries
Authors: Holzer Ralf J. , Gauvreau Kimberlee , Kreutzer Jacqueline , Leahy Ryan , Murphy Joshua , Lock James E. , Cheatham John P. , Bergersen Lisa
Published: April 2011

Background—

Pulmonary artery (PA) balloon angioplasty and/or stenting (PA rehabilitation) is one of the most common procedures performed in the cardiac catheterization laboratory, but comprehensive and consistently reported data on procedure-related adverse events (AE) are scarce.

Methods and Results—

Data were prospectively collected using a multicenter registry (Congenital Cardiac Catheterization Project on Outcomes). All cases that included balloon angioplasty and/or stent implantation in a proximal or lobar PA position were included. Multivariate analysis was used to evaluate for independent predictors of AE and need for early reintervention. Between February 2007 and December 2009, 8 institutions submitted details on 1315 procedures with a PA intervention. An AE was documented in 22% with a high severity (level 3 to 5) AE in 10% of cases. Types of AE included vascular/cardiac trauma (19%), technical AE (15%), arrhythmias (15%), hemodynamic AE (14%), bleeding via endotracheal tube/reperfusion injury (12%), and other AE (24%). AE were classified as not preventable in 50%, possibly preventable in 41%, and preventable in 9%. By multivariate analysis, independent risk factors for level 3 to 5 AE were presence of ≥2 indicators of hemodynamic vulnerability, age below 1 month, use of cutting balloons, and operator experience of <10 years. Reintervention during the study period occurred in 22% of patients undergoing PA rehabilitation.

Conclusions—

PA rehabilitation is associated with a 10% incidence of high-level severity AE. Hemodynamic vulnerability, young age, use of cutting balloons, and lower operator experience were significant independent risk factors for procedure-related AE.
One-Year Clinical Outcome of Interventionalist- Versus Patient-Transfer Strategies for Primary Percutaneous Coronary Intervention in Patients With Acute ST-Segment Elevation Myocardial Infarction
Authors: Zhang Qi , Zhang Rui Yan , Qiu Jian Ping , Zhang Jun Feng , Wang Xiao Long , Jiang Li , Liao Min Lei , Zhang Jian Sheng , Hu Jian , Yang Zheng Kun , Shen Wei Feng
Published: April 2011

Background—

Traditional reperfusion options for patients with acute ST-segment elevation myocardial infarction (STEMI) presenting to non-primary percutaneous coronary intervention (PPCI)-capable hospitals generally include onsite fibrinolytics or emergency transfer for PPCI. A third option, involving interventionalist transfer, was examined in the REVERSE-STEMI study.

Methods and Results—

A total of 334 patients with acute STEMI who presented to 5 referral hospitals with angiographic facilities but without interventionalists qualified for PPCI were randomized to receive PPCI with either an interventionalist- (n=165) or a patient-transfer (n=169) strategy. The primary end point of door-to-balloon (D2B) time and secondary end points of left ventricular ejection fraction and major adverse cardiac events (MACE) at 1-year clinical follow-up were compared between the 2 groups. Compared with the patient-transfer strategy, the interventionalist-transfer strategy resulted in a significantly shortened D2B time (median, 92 minutes versus 141 minutes;
P
<0.0001), with more patients having first balloon angioplasty within 90 minutes (21.2% versus 7.7%,
P
<0.001). This treatment strategy also was associated with higher left ventricular ejection fraction (0.60±0.07 versus 0.57±0.09,
P
<0.001) and improved 1-year MACE-free survival (84.8% versus 74.6%,
P
=0.019). Multivariate Cox proportional hazards modeling revealed that the interventionalist-transfer strategy was an independent factor for reduced risk of composite MACE (hazard ratio, 0.63; 95% CI, 0.45 to 0.88;
P
=0.003).

Conclusions—

The interventionalist-transfer strategy for PPCI may be effective in improving the care of patients with STEMI presenting to a non-PPCI-capable hospital, particularly in a congested cosmopolitan region where patient transfers could be prolonged.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00713557.
Precipitation Bragg Scatter in Radar Observations at Nadir
Authors: Jameson A. R.
Published: April 2011

As precipitation sediments and interacts with turbulence, spatial structures appear as the familiar “streamers” of precipitation sweeping across the road during a thunderstorm or like those so obvious in snow that is backlit. Some of these are at scales that resonate with the radar wavelength, and as a consequence they produce coherent backscatter (precipitation Bragg scatter). Recently, and in contrast to incoherent scattering, it was found that the power-normalized cross-correlation functions of backscattered complex amplitudes in neighboring range bins ρ12 averaged over time exist. Moreover, they are identical to the fractional contributions made by radar coherent backscatter in the radial direction to the total backscattered power in rain and snow. This coherent power can significantly affect some radar techniques for measuring precipitation intensity because it depends upon the square of the particle concentrations rather than the linear dependence in the case of incoherent backscatter. All of these observations were made by radars looking tangentially to the ground, however. Yet for many purposes, including the global measurements of precipitation from space, radar observations in precipitation are at or near nadir to the surface of the earth. A natural question, then, is: Can coherent backscattered power be found in observations in precipitation at nadir as well? Here, radar observations collected at nadir in a convective shower and snow are analyzed. It is found that ρ12 and, hence, precipitation Bragg scatter exist in these nadir observations. Moreover, the intensity of the Bragg scatter is independent of the size of sample volume. Reasons for these findings and some implications are discussed.