Significance of histologic pattern of carcinoma and sarcoma components on survival outcomes of uterine carcinosarcoma.

BACKGROUND: To examine the effect of the histology of carcinoma and sarcoma components on survival outcome of uterine carcinosarcoma. PATIENTS AND METHODS: A multicenter retrospective study was conducted to examine uterine carcinosarcoma cases that underwent primary surgical staging. Archived slides were examined and histologic patterns were grouped based on carcinoma (low-grade versus high-grade) and sarcoma (homologous versus heterologous) components, correlating to clinico-pathological demographics and outcomes. RESULTS: Among 1192 cases identified, 906 cases were evaluated for histologic patterns (carcinoma/sarcoma) with high-grade/homologous (40.8%) being the most common type followed by high-grade/heterologous (30.9%), low-grade/homologous (18.0%), and low-grade/heterologous (10.3%). On multivariate analysis, high-grade/heterologous (5-year rate, 34.0%, P = 0.024) and high-grade/homologous (45.8%, P = 0.017) but not low-grade/heterologous (50.6%, P = 0.089) were independently associated with decreased progression-free survival (PFS) compared with low-grade/homologous (60.3%). In addition, older age, residual disease at surgery, large tumor, sarcoma dominance, deep myometrial invasion, lymphovascular space invasion, and advanced-stage disease were independently associated with decreased PFS (all, P < 0.01). Both postoperative chemotherapy (5-year rates, 48.6% versus 39.0%, P < 0.001) and radiotherapy (50.1% versus 44.1%, P = 0.007) were significantly associated with improved PFS in univariate analysis. However, on multivariate analysis, only postoperative chemotherapy remained an independent predictor for improved PFS [hazard ratio (HR) 0.34, 95% confidence interval (CI) 0.27-0.43, P < 0.001]. On univariate analysis, significant treatment benefits for PFS were seen with ifosfamide for low-grade carcinoma (82.0% versus 49.8%, P = 0.001), platinum for high-grade carcinoma (46.9% versus 32.4%, P = 0.034) and homologous sarcoma (53.1% versus 38.2%, P = 0.017), and anthracycline for heterologous sarcoma (66.2% versus 39.3%, P = 0.005). Conversely, platinum, taxane, and anthracycline for low-grade carcinoma, and anthracycline for homologous sarcoma had no effect on PFS compared with non-chemotherapy group (all, P > 0.05). On multivariate analysis, ifosfamide for low-grade/homologous (HR 0.21, 95% CI 0.07-0.63, P = 0.005), platinum for high-grade/homologous (HR 0.36, 95% CI 0.22-0.60, P < 0.001), and anthracycline for high-grade/heterologous (HR 0.30, 95% CI 0.14-0.62, P = 0.001) remained independent predictors for improved PFS. Analyses of 1096 metastatic sites showed that carcinoma components tended to spread lymphatically, while sarcoma components tended to spread loco-regionally (P < 0.001). CONCLUSION: Characterization of histologic pattern provides valuable information in the management of uterine carcinosarcoma.

Kinematics of aquatic and terrestrial prey capture in Terrapene carolina, with implications for the evolution of feeding in cryptodire turtles.

Studies of aquatic prey capture in vertebrates have demonstrated remarkable convergence in kinematics between diverse vertebrate taxa. When feeding in water, most vertebrates employ large-amplitude hyoid depression to expand the oral cavity and suck in water along with the prey. In contrast, vertebrates feeding on land exhibit little or no hyoid depression. In this study we compared the kinematics of terrestrial and aquatic prey capture within one species of turtle, Terrapene carolina, in order to determine whether an individual species can modulate the magnitude of hyoid depression between air and water. High-speed video (250 frames per second) showed that hyoid depression was over three times greater in aquatic than in terrestrial feedings, indicating that T. carolina is able to modulate hyoid depression magnitude depending on the medium in which feeding occurs. In addition, we observed medium-dependent modulation of hyoid depression in another turtle, Heosemys grandis, and large-amplitude hyoid depression during aquatic feeding in Kinosternon leucostomum, Platysternon megacephalum, and juvenile Chelydra serpentina. In all of these turtles, hyoid depression produced oral cavity expansion during aquatic feeding, but the earthworm prey were never sucked toward the predators. Prey were captured by neck extension (ram feeding), and we conclude that the function of hyoid depression during aquatic feeding in cryptodire turtles is to prevent the forward motion of the predator from pushing the prey away (compensatory suction). Aquatic feeding is probably the primitive condition for all extant turtles, and thus terrestrial feeding in T. carolina and other turtles is a secondarily derived characteristic. We conclude from this historical pattern that it is not appropriate to use extant turtles in attempts to reconstruct the terrestrial feeding mechanisms of primitive amniotes.