Citations

Purpose To evaluate clinical characteristics and survival outcomes among patients with locally advanced or metastatic colorectal cancer who achieve a complete response (CR) to systemic treatment either alone or with multimodality approach. Patients and Methods Data were collected retrospectively from CRC patients enrolled onto the phase III trial N9741, a National Cancer Institute–funded and Gastrointestinal Cancer Intergroup–sponsored study coordinated by the North Central Cancer Treatment Group. Patients were randomly assigned to combinations of oxaliplatin, fluorouracil (FU)/leucovorin (LV) and irinotecan. The three treatment arms consist of IFL (irinotecan + FU/LV), FOLFOX4 (oxaliplatin + FU/LV), and IROX (irinotecan + oxaliplatin). Median follow-up was 42.6 months. Results Sixty-two (4%) of 1,508 patients had a CR to chemotherapy alone, and an additional 32 (2%) had a CR after multimodality treatment. Factors associated with achieving CR with systemic chemotherapy alone included FOLFOX4 treatment, patients with assessable disease, or a single site of metastasis. Continuing protocol treatment beyond two cycles after documentation of CR was not associated with improved survival. The rate of curative intent resection was significantly higher for patients treated with oxaliplatin-containing regimens (P = .02). Median survival was similar between patients with CR after chemotherapy alone (44.3 months) or after multimodality approach (47.4 months; P = .81). Conclusion FOLFOX4 was more likely to produce a CR than were IFL or IROX. Oxaliplatin regimens were more likely to result in successful surgical resections. Patients who have CR to systemic chemotherapy alone can achieve impressive survival outcomes similar to those seen among patients who attained a CR status after multimodality treatment.

Abstract Chronic lymphocytic leukemia (CLL) and other B-cell lymphoproliferative disorders display familial aggregation. To identify a susceptibility gene for CLL, we assembled families from the major European (ICLLC) and American (GEC) consortia to conduct a genome-wide linkage analysis of 101 new CLL pedigrees using a high-density single nucleotide polymorphism (SNP) array and combined the results with data from our previously reported analysis of 105 families. Here, we report on the combined analysis of the 206 families. Multipoint linkage analyses were undertaken using both nonparametric (model-free) and parametric (model-based) methods. After the removal of high linkage disequilibrium SNPs, we obtained a maximum nonparametric linkage (NPL) score of 3.02 (P = .001) on chromosome 2q21.2. The same genomic position also yielded the highest multipoint heterogeneity LOD (HLOD) score under a common recessive model of disease susceptibility (HLOD = 3.11; P = 7.7 × 10−5), which was significant at the genome-wide level. In addition, 2 other chromosomal positions, 6p22.1 (corresponding to the major histocompatibility locus) and 18q21.1, displayed HLOD scores higher than 2.1 (P < .002). None of the regions coincided with areas of common chromosomal abnormalities frequently observed in CLL. These findings provide direct evidence for Mendelian predisposition to CLL and evidence for the location of disease loci.

Abstract Immune reactivity to self-antigens in both cancer and autoimmune diseases can be enhanced by systemic immune modulation, posing a challenge in cancer immunotherapy. To distinguish the genetic and immune regulation of tumor immunity versus autoimmunity, immune responses to human ErbB-2 (Her-2) and mouse thyroglobulin (mTg) were tested in transgenic mice expressing Her-2 that is overexpressed in several cancers, and HLA-DRB1*0301 (DR3) that is associated with susceptibility to several human autoimmune diseases, as well as experimental autoimmune thyroiditis (EAT). To induce Her-2 response, mice were electrovaccinated with pE2TM and pGM-CSF encoding the extracellular and transmembrane domains of Her-2 and the murine granulocyte macrophage colony-stimulating factor, respectively. To induce EAT, mice received mTg i.v. with or without lipopolysaccharide. Depletion of regulatory T cells (Treg) with anti-CD25 monoclonal antibody enhanced immune reactivity to Her-2 as well as mTg, showing control of both Her-2 and mTg responses by Treg. When immunized with, Her-2xDR3 and B6xDR3 mice expressing H2bxDR3 haplotype developed more profound mTg response and thyroid pathology than Her-2 or B6 mice that expressed the EAT-resistant H2b haplotype. In Her-2xDR3 mice, the response to mTg was further amplified when mice were also immunized with pE2TM and pGM-CSF. On the contrary, Her-2 reactivity was comparable whether mice expressed DR3 or not. Therefore, induction of Her-2 immunity was independent of DR3 but development of EAT was dictated by this allele, whereas Tregs control the responses to both self-antigens. These results warrant close monitoring of autoimmunity during cancer immunotherapy, particularly in patients with susceptible MHC class II alleles. [Cancer Res 2007;67(14):7020–7]

Studies of the immunohistochemical profiles and clinical course of desmoplastic melanoma have produced conflicting results. We identified 28 cases of desmoplastic melanoma after a search of our files for spindle cell neoplasms of the head and neck from 1960 through 1995. The 17 male (61%) and 11 female (39%) patients averaged 65 years of age. The cheek was the most common location (12 cases, 43%). The average length of follow-up was 5 years. Overall 5-year survival rate was 46%. Melan A and tyrosinase positivity (P = 0.0195), smooth muscle actin positivity (P = 0.0328), tumor size (P = 0.0297), and tumor thickness (P = 0.0419) were significantly associated with local progression-free survival. No histologic or immunohistochemical marker was associated with overall or metastasis-free survival.

The goals of this study were to evaluate the validity of the visual analogue scale (VAS) for young children and to compare a newly developed method of teaching children to use a VAS with one used in our previous studies. It was hypothesized that the new method would increase the number of children who understand the VAS and correctly mark their responses on the VAS line. The association between child's age and ability to understand the VAS was also evaluated. One hundred-six children with a laceration requiring sutures and receiving a lidocaine injection for local anesthesia participated in the study. They ranged in age from 5 to 14 years. Two outcome measures were used to assess the baseline and lidocaine injection pain: a 5-point Likert scale and a VAS. A calibration study was used to determine whether the subjects were able to use the VAS to make proportional judgments about their perceptions. Teaching method had no effect on the number of subjects who could correctly mark their responses on the VAS line, nor did it significantly increase the number of subjects who could understand the concept of the VAS. Subjects who were able to understand the VAS were significantly older (mean = 9.8 years, SD = 2.8) than those who did not (mean = 8.2 years, SD = 2.5). Overall, only about one third of the subjects were able to correctly mark the VAS and understand the concept of the VAS. Other measures of pain that are better understood by young children may be more valid indicators of pain than the VAS.

The stabilizing capacity of the ligaments and articular surface in the ankle was determined under defined physiologic loading conditions. The concept of primary and secondary constraints was adapted to the ankle. With physiologic loading, the articular surface ac counted for 30% and 100% of stability in rotation and version, respectively. That the articular surface was the sole source of inversion and eversion stability under the prescribed physiologic loading conditions has not been previously reported. The demonstration that the articular surface resists inversion displacement in the loaded ankle supports the conclusion of previous studies that rotation, rather than inversion, may account for a type of clinically sympto matic ankle instability. Further, ankle instability may occur during loading and unloading but not once the ankle is fully loaded. The results of our study confirm the importance of the anterior talofibular and calcaneo fibular ligaments and suggest an important role for the deltoid ligament.

Purpose Atypical hyperplasia is a well-recognized risk factor for breast cancer, conveying an approximately four-fold increased risk. Data regarding long-term absolute risk and factors for risk stratification are needed. Patients and Methods Women with atypical hyperplasia in the Mayo Benign Breast Disease Cohort were identified through pathology review. Subsequent breast cancers were identified via medical records and a questionnaire. Relative risks (RRs) were estimated using standardized incidence ratios, comparing the observed number of breast cancers with those expected based on Iowa Surveillance, Epidemiology, and End Results (SEER) data. Age, histologic factors, and family history were evaluated as risk modifiers. Plots of cumulative breast cancer incidence provided estimates of risk over time. Results With mean follow-up of 13.7 years, 66 breast cancers (19.9%) occurred among 331 women with atypia. RR of breast cancer with atypia was 3.88 (95% CI, 3.00 to 4.94). Marked elevations in risk were seen with multifocal atypia (eg, three or more foci with calcifications [RR, 10.35; 95% CI, 6.13 to 16.4]). RR was higher for younger women (< 45; RR, 6.76; 95% CI, 3.24 to 12.4). Risk was similar for atypical ductal and atypical lobular hyperplasia, and family history added no significant risk. Breast cancer risk remained elevated over 20 years, and the cumulative incidence approached 35% at 30 years. Conclusion Among women with atypical hyperplasia, multiple foci of atypia and the presence of histologic calcifications may indicate “very high risk” status (> 50% risk at 20 years). A positive family history does not further increase risk in women with atypia.