Between April 1981 and December 1983, patients with locoregional carcinoma of the nasopharynx were treated with two courses of chemotherapy administered before radiation therapy. Chemotherapy consisted of methotrexate, bleomycin, and cisplatin, which were administered at 3-week intervals, and radiation therapy was scheduled to commence 3 weeks after the start of the second course. Forty-nine of 51 consecutive patients were treated; only one patient progressed on chemotherapy, and of 36 patients with measurable neck nodes, eight had complete and 19 had partial clearance (greater than 50% decrease in cross-sectional area) of these nodes when assessed before initiation of radiotherapy. Despite the high rate of tumor response (75%; 95% confidence limits, 59% to 91%), the actuarial survival and disease-free survival curves were almost identical to those recorded for a consecutive group of 140 historical controls of similar stage distribution treated with radiation alone. This chemotherapy provided a high rate of tumor remission, but did not appear to convey long-term benefit to patients when used before radiation therapy.

The routine use of high-dose opioids for analgesia in patients with acute burns and soft-tissue injuries often leads to the development of opioid-induced constipation. The opioid antagonist methylnaltrexone (MLTX) reverses narcotic-related ileus without affecting systemic pain treatment. The authors' burn center developed a bowel protocol that included administration of MLTX for relief of opioid-induced constipation after other methods failed. The authors performed a retrospective review of patients with acute burns or necrotizing soft-tissue infections, who had been given subcutaneous MLTX to induce laxation. All patients who received MLTX were included and all administrations of the drug were included in the analysis. The primary outcome examined was time to laxation from drug administration. Forty-eight patients received MLTX a total of 112 times. Six patients were admitted with soft-tissue injuries and the rest suffered burns with an average TBSA of 17%. The median patient age was 41 years and the majority (75%) were men. Administration of a single dose of MLTX resulted in laxation within 4 hours in 38% of cases, and within 24 hours in 68%. Patients given MLTX received an average of 174 mg morphine equivalents daily for pain control. MLTX was given after an average of 52 hours since the last bowel movement. As this experience has evolved, it has been incorporated into an organized bowel protocol, which includes MLTX administration after other laxatives have failed. MLTX is an effective laxation agent in patients with burn and soft-tissue injuries, who have failed conventional agents.

There has been a tremendous evolution in our thinking about cancer since the 1880s. Breast cancer is a particularly good example to evaluate the progress that has been made and the new challenges that have arisen due to screening that inadvertently identifies indolent lesions. The degree to which overdiagnosis is a problem depends on the reservoir of indolent disease, the disease heterogeneity, and the fraction of the tumors that have aggressive biology. Cancers span the spectrum of biological behavior, and population-wide screening increases the detection of tumors that may not cause harm within the patient's lifetime or may never metastasize or result in death. Our approach to early detection will be vastly improved if we understand, address, and adjust to tumor heterogeneity. In this article, we use breast cancer as a case study to demonstrate how the approach to biological characterization, diagnostics, and therapeutics can inform our approach to screening, early detection, and prevention. Overdiagnosis can be mitigated by developing diagnostics to identify indolent disease, incorporating biology and risk assessment in screening strategies, changing the pathology rules for tumor classification, and refining the way we classify precancerous lesions. The more the patterns of cancers can be seen across other cancers, the more it is clear that our approach should transcend organ of origin. This will be particularly helpful in advancing the field by changing both our terminology for what is cancer and also by helping us to learn how best to mitigate the risk of the most aggressive cancers.See all articles in this CEBP Focus section, "NCI Early Detection Research Network: Making Cancer Detection Possible."

In this analysis, subjects considered as high-risk patients were more likely to require an FT than low-risk patients. Assessment of preoperative risk factors may improve decision making for selective intraoperative FT placement.

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Background: Surgical treatment of invasive lobular carcinoma (ILC) is challenging due to its diffuse growth pattern, and the positive margin rate after mastectomy is poorly described. Methods: We retrospectively determined the positive margin rate in those with stage I-III ILC undergoing mastectomy. We evaluated the relationship between management strategy and recurrence free survival (RFS). Results: In 357 patients, the positive margin rate was 10.6% overall and 18.7% in those with T3 tumors. Having a positive margin was associated with significantly shorter RFS on multivariate analysis (p ¼ 0.01). Undergoing additional local treatment (radiation or re-excision) for a positive margin was significantly associated with improved RFS (p ¼ 0.004). Older women with positive margins were significantly less likely to undergo additional local therapy. Conclusions: Even mastectomy fails to clear margins in a high proportion of patients with large ILC tumors, a finding which may warrant testing neoadjuvant strategies even prior to planned mastectomy.

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