Tumor-related prognostic factors for breast cancer

Interest in prognostic factors for breast cancer has been stimulated by the success of systemic adjuvant therapy for early-stage operable disease. Patients destined for recurrence can be selected for systemic adjuvant therapy, while patients not likely to recur can be spared the morbidity of unnecessary treatment. The number of tumor-related features available for prognosis has grown impressively in recent years. The purpose of this article is to review tumor-related biologic factors and relate them to prognosis and treatment objectives.     

Primary coexistent adenocarcinoma and choriocarcinoma of the stomach. A case report and review of the literature

We report a case of primary gastric choriocarcinoma with liver metastasis. The mixed histologic patterns included adenocarcinoma, undifferentiated carcinoma, and choriocarcinoma. Immunohistologic staining for the beta-subunit of human chorionic gonadotrophin (beta-HCG) showed positive results in the choriocarcinoma, adenocarcinoma, and normal mucosal gland. However, positive HCG cells were present at different intensities in the choriocarcinoma, adenocarcinoma, and normal mucosal gland. The level of HCG was significantly increased in serum. This unusual tumor probably resulted from dedifferentiation of a primary adenocarcinoma or developed directly from the mucosal glands.     

The functional outcome of lower-extremity fractures with vascular injury

Salvage of lower-extremity Gustilo type IIIC fractures is difficult, time-consuming for the patients and physicians, and not universally successful because of poor functional outcomes. Even if successful with limb salvage, the functional result may be unsatisfactory because of mutilating injuries to muscle and nerve, bone loss, and the presence of chronic infection. From July 1991 until July 1994, revascularizations of open IIIC fractures were attempted for wounds with Mangled Extremity Severity Score (MESS) < or = 10. The functional results were evaluated at 2 years after injury. Thirty-six lower-extremity revascularizations were performed on 34 patients, including 1 patient with bilateral distal tibial IIIC fractures and a child with IIIC femoral fracture accompanied by ipsilateral distal tibial amputation. Excluded were patients with below-ankle IIIC fractures as well as patients who underwent immediate amputation at admission. After the revascularization, seven patients with IIIC fractures (7 of 36, 19.4%) underwent secondary amputation within 1 week. At the 2-year follow-up, the overall secondary amputation rate was 25% (9 of 36) and the salvage rate was 75% (27 of 36). Those were no deaths. Of the 29 salvaged limbs among these 27 patients, 23 limbs (23 of 29, 79.3%) required secondary coverage procedures that included 12 free flap transfers (12 of 29, 41.4%). Every patient needed subsequent reconstructive surgery to achieve an acceptable functional result. In this series, MESS was able to predict the secondary amputation rate and the functional result. Sixteen of the 17 limb-salvaged patients with MESS < or = 7 were able to achieve minimal functional requirements, whereas 3 of the 10 patients with MESS = 8 to 10 failed to achieve minimal functional requirements at the 2-year follow-up. Using statistical analysis, we found that the salvaged limbs with MESS < or = 9 exhibited a significant difference in achieving adequate function compared with limbs with MESS > 9. Using our protocol for treatment for IIIC fractures, the threshold for immediate amputation can be raised from MESS = 7 to MESS = 9. Our conclusions are (1) more severely injured limbs have poor functional results, (2) every patient needs subsequent reconstructive surgery, and (3) the MESS may be helpful in decision-making.     

Cell cycle-dependent establishment of a late replication program

DNA replication origins in chromosomes of eukaryotes are activated according to a temporal program. In the yeast Saccharomyces cerevisiae, activation of origins in early S phase appears to be a default state. However, cis-acting elements such as telomeres can delay origin activation until late S phase. Site-specific recombination was used to separate origin from telomere in vivo, thereby demonstrating that the signal for late activation is established between mitosis and START in the subsequent G1 phase. Once set, the signal can persist through the next S phase in the absence of the telomere. Establishment of the temporal program and of initiation competence of origins may be coincident events.