Citations

AbstractApproximately 5% of rectal cancers are locally advanced with adherence to the vagina, uterus, bladder, prostate, or other structures. Sacral involvement is fortunately rare in primary cancers. In about 50% of patients there is histologic confirmation of tumor invasion in the area of adherence. It is important to recognize the nature of these tumors pre‐operatively so that the patient can be prepared for an exenterative procedure should this be necessary. When these tumors are removeden bloc, 5‐year survival rates of 50% can be obtained with survival depending on the presence or absence of regional metastasis and also the presence or absence of histologic tumor invasion into adjacent structures.

AbstractWide dissection of adenocarcinoma of the rectum is difficult because of the fixed structure of the anatomic pelvis. The role of lateral margins, excision of the mesorectum, and extended lymphadenectomy have recently received much attention in the literature in dealing surgically with more advanced rectal carcinomas. The basic question to be resolved in the future is whether additional radical surgery is of more benefit than adjuvant chemoradiation therapy in this setting.

AbstractPer anal excision is suitable for rectal carcinoma that is <3 cm and has not invaded into the muscular layer of the rectum. The upper margin of the lesion should not be >7 cm from the anal verge. The entire lesion is excised in its full thickness with a 1.5 cm to 2 cm normal margin, using electrocautery. It is important that the specimen is carefully examined by the pathologist for completeness of the excision and grade of the carcinoma. Abdominoperineal resection should be considered in good risk patients if adequate margins cannot be achieved and if the carcinoma is a high pathologic grade.

Purpose To evaluate the impact of letrozole compared with placebo after adjuvant tamoxifen on quality of life (QOL) in the MA.17 trial. Methods Patients completed the Short Form 36-item Health Survey (SF-36) and the Menopause Specific Quality of Life Questionnaire (MENQOL) at baseline, 6 months, and annually. Mean change scores from baseline were compared between groups for summary measures and domains. A response analysis compared the proportion of patients who demonstrated an important change in QOL. Results Of 5,187 randomly assigned women in the trial, 3,612 (69.9%) participated in the QOL substudy: 1,799 were allocated to placebo and 1,813 were allocated to letrozole. No differences were seen between groups in mean change scores from baseline for the SF-36 physical and mental component summary scores at 6, 12, 24, and 36 months. Small (< 0.2 standard deviations) but statistically significant differences in mean change scores from baseline were seen for the SF-36 domains of physical functioning (12 months), bodily pain (6 months) and vitality (6 and 12 months), and the MENQOL vasomotor (6, 12, and 24 months) and sexual domains (12 and 24 months). On the response analysis, a significant difference was seen between groups for the bodily pain domain (percentage of patients reporting a worsening of QOL, 47% placebo v 51% letrozole; P = .009) and the vasomotor domain (22% placebo v 29% letrozole; P = .001). Conclusion Letrozole did not have an adverse impact on overall QOL. Small effects were seen in some domains consistent with a minority of patients experiencing changes in QOL compatible with a reduction in estrogen synthesis.

Epigenetic inheritance of heterochromatin structure is an important cellular process whose mechanism remains elusive. In this article, we describe the identification of nine enhancers of the silencing defect of a Saccharomyces cerevisiae -PCNA mutant by screening a library of ≈4,700 viable yeast deletion mutants. Of the nine mutants identified, six ( hir1 , hir3 , sas2 , sas4 , sas5 , and sir1 ) were previously known to reduce silencing synergistically with a mutation in Cac1p, the large subunit of chromatin assembly factor 1 (CAF-1). The predicted gene products that are affected in three other mutants ( nam7 , msh2 , and rtt106 ) have not been implicated previously in silencing. Characterization of the rtt106 Δ allele revealed that it synergistically reduced heterochromatin silencing when combined with a mutation in Cac1p but not with a mutation in Asf1p (a histone H3 and H4 chaperone). Moreover, Rtt106p interacted with histones H3 and H4 both in vitro and in vivo , and it displayed a nucleosome assembly activity in vitro . Furthermore, Rtt106p interacts with CAF-1 physically through Cac1p. These biochemical and genetic data indicate that Rtt106p is a previously uncharacterized histone chaperone connecting S phase to epigenetic inheritance.

This Resource Letter provides a guide to the literature on medical imaging, with emphasis on magnetic resonance imaging. The letter E after an item indicates elementary level of material of general interest to persons becoming informed in the field. The letter I, for intermediate level, indicates material of somewhat more specialized nature; and the letter A indicates rather specialized or advanced material.

SummaryImmunity to measles is conferred by the interplay of humoral and cellular immune responses, the latter being critical in maintaining long-term recall response. Therefore, it is important to evaluate measles-specific humoral and cellular immunity in populations several years after vaccination and understand the correlations among these measures of immunity. We examined measles-specific antibodies, lymphoproliferation and the Th1/Th2 signature cytokines, interferon (IFN)-γ and interleukin (IL)-4, in a population-based cohort of healthy children from Olmsted County, Minnesota after two doses of measles–mumps–rubella-II (MMR-II) vaccine. We detected positive measures of measles-specific cellular and humoral immunity in the majority of our study population. However, a small proportion of subjects demonstrated an immune response skewed towards the Th2 type, characterized by the presence of either IL-4 and/or measles-specific antibodies and a lack of IFN-γ production. Further, we observed a significant positive correlation between lymphoproliferation and secretion of IFN-γ (r = 0·20, P = 0·0002) and IL-4 (r = 0·15, P = 0·005). Measles antibody levels were correlated with lymphoproliferation (r = 0·12, P = 0·03), but lacked correlation to either cytokine type. In conclusion, we demonstrated the presence of both long-term cellular and humoral responses after MMR-II vaccination in a significant proportion of study subjects. Further, a positive correlation between lymphoproliferation and IL-4 and IFN-γ suggests that immunity to measles may be maintained by both Th1 and Th2 cells. We speculate that the Th2 biased response observed in a subset of our subjects may be insufficient to provide long-term immunity against measles. Further examination of the determinants of Th1 versus Th2 skewing of the immune response and long-term follow-up is needed.

Mantle-cell lymphoma (MCL) is now recognized as a distinct clinicopathologic subtype of B-cell non-Hodgkin's lymphoma. Patients with MCL are typically older adults with a male predominance and usually present with stage IV disease. The cells are characterized as CD20+ CD5+ CD23− with a t(11;14)(q13;q32) and cyclin D1 overexpression on immunohistochemistry. Response to chemotherapy usually results in a tumor response but unmaintained remissions are short and the median survival is 3 to 4 years. The treatment approach to newly diagnosed patients with MCL depends on the patient's eligibility for stem cell transplantation (SCT). Those who are eligible are usually treated with either rituximab-CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) followed by SCT or rituximab-HyperCVAD (cyclophosphamide, vincristine, doxorubicin, decadron, cytarabine, and methotrexate) followed by observation. The purine nucleoside analogues also have activity as single agents and with rituximab. Unfortunately none of these approaches can definitively cure patients with MCL, and new agents are needed. Recent studies in patients with relapsed MCL have shown substantial antitumor activity of single-agent bortezomib, single-agent temsirolimus, and the combination of thalidomide and rituximab. Studies integrating these novel agents earlier in the disease course or in combination with each other will hopefully produce more durable responses with less toxicity.