Citations

AbstractSurgical resection continues to be the primary curative modality for patients with adenocarcinoma of the rectum. However, local tumor recurrence in the pelvis and/or distant metastasis may occur in spite of complete excision of grossly visible malignant disease. Surgical and pathologic staging can identify a subset of surgically treated rectal cancer patients at high risk for tumor relapse and death. Irradiation and chemotherapy have been used as adjuvant therapy in conjunction with surgery as single modalities and in combination for patients with high risk rectal cancer. Evidence from controlled clinical trials indicates a significant decrease in local tumor recurrence, and a significant improvement in disease‐free and overall survival with the use of combined postoperative irradiation and chemotherapy in this setting. A current national clinical trial in the United States of America is studying whether irradiation can be combined with new chemotherapy regimens which have shown significant therapeutic benefit as surgical adjuvant therapy for patients with high risk colon cancer (5FU + levamisole) and for patients with metastatic colorectal cancer (5FU + leucovorin) to further improve the efficacy of surgical adjuvant therapy for adenocarcinoma of the rectum.

AbstractUseful palliation can often be achieved when standard treatment approaches of external beam irradiation and chemotherapy with or without resection are used for locally advanced primary rectal malignancies. Local control and long‐term survival are achieved in only 10% to 50% of patients, however, due to the limited irradiation tolerance of surrounding organs and tissues. Encouraging trends exist in separate intra‐operative irradiation analyses from Massachusetts General Hospital and Mayo Clinic with regard to improvement in local control and possibly survival of locally advanced rectal lesions, warranting continued evaluation of such approaches. Disease control within the intra‐operative and external irradiation field is decreased, however, when the surgeon is unable to accomplish gross total resection. Therefore it seems reasonable to consistently add 5‐Fluorouracil with or without Leucovorin during external irradiation and to evaluate the use of dose modifiers, such as sensitizers or hyperthermia, in conjunction with intra‐operative irradiation. Since high systemic failure rates exist with both locally advanced primary and recurrent lesions, more effective chemotherapy needs to be evaluated during external irradiation as well as after completion of such. In view of survival advantages with 5‐Fluorouracil plus Leucovorin versus 5‐Fluorouracil alone for metastatic disease, this regimen is currently being employed. Even with locally recurrent lesions, the aggressive multimodality approaches including intra‐operative irradiation have resulted in improved local control, and long‐term survival rates of 20% to 25% versus an expected 5% with conventional techniques in historical series.

AbstractRelapses after “curative resection” of rectal cancer may be localized and thus amenable to surgical treatment. The risk of relapse may be higher than previously believed depending on adequacy and length of follow‐up, the diagnostic modalities used, and the number of autopsies performed. Technical refinements such as a distal margin >2 cm, radical pelvic lymphadenectomy, and high ligation of the inferior mesenteric artery at the aorta do not appear to diminish the risk of recurrence. A wider lateral margin and a more complete excision of the mesorectum may be beneficial, but this is yet unproven. Surgery for isolated, locally recurrent lesions should be limited to carefully selected patients and performed in tertiary centers using a team approach. Whether such radical “salvage” procedures are justifiable merits further careful evaluation.

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.