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Background: Urokinase-type plasminogen activator (uPA) and its inhibitor (PAI-1) play essential roles in tumor invasion and metastasis. High levels of both uPA and PAI-1 are associated with poor prognosis in breast cancer patients. To confirm the prognostic value of uPA and PAI-1 in primary breast cancer, we reanalyzed individual patient data provided by members of the European Organization for Research and Treatment of Cancer-Receptor and Biomarker Group (EORTC-RBG). Methods: The study included 18 datasets involving 8377 breast cancer patients. During follow-up (median 79 months), 35% of the patients relapsed and 27% died. Levels of uPA and PAI-1 in tumor tissue extracts were determined by different immunoassays; values were ranked within each dataset and divided by the number of patients in that dataset to produce fractional ranks that could be compared directly across datasets. Associations of ranks of uPA and PAI-1 levels with relapse-free survival (RFS) and overall survival (OS) were analyzed by Cox multivariable regression analysis stratified by dataset, including the following traditional prognostic variables: age, menopausal status, lymph node status, tumor size, histologic grade, and steroid hormone-receptor status. All P values were two-sided. Results: Apart from lymph node status, high levels of uPA and PAI-1 were the strongest predictors of both poor RFS and poor OS in the analyses of all patients. Moreover, in both lymph node-positive and lymph node-negative patients, higher uPA and PAI-1 values were independently associated with poor RFS and poor OS. For (untreated) lymph node-negative patients in particular, uPA and PAI-1 included together showed strong prognostic ability (all P

A total of 144 evaluable patients with breast cancer were enrolled in a multicenter, randomized, prospective study to establish the role of delayed shoulder exercises on wound drainage and shoulder function after axillary lymph node dissection. Patients in group 1 (n = 78) started active shoulder exercises 1 day postoperatively. Patients in group 2 (n = 66) started on the eight postoperative day, following 1 week of immobilization of the arm. Patients in group 2 had 14% less wound drainage volume than those in group 1 (600 [+ or -] 436 mL versus 701 [+ or -] 398 mL); this difference, however, was not significant. Also, no differences could be established between the two groups when duration and volume of wound drainage, number and volume of wound drainage, number and volume of seroma aspirations, would complication rates, and shoulder function were compared 6 months after surgery., The most common cancer in women is breast cancer, occurring in about 9 percent of the female population. Treatment for this cancer may include breast resection (removal of all or a significant portion of the breast) and dissection of the lymph nodes of the axilla (arm pit). The most common postoperative complication is development of lymphedema (accumulation of lymph in the soft tissues); inadequate function of the shoulder may also result. Postoperative care for these complications is controversial. Some physicians recommend shoulder exercises immediately after surgery, but others suggest that these early exercises reduce the desired drainage from the wound. In order to evaluate the effects of early exercise, a prospective randomized study was undertaken of 144 patients with breast cancer. All patients, those having modified radical mastectomy as well as those having breast conserving treatment, underwent axillary lymph node dissection. One group of 78 women began active shoulder exercises one day following surgery; the second group, 66 women, began exercises on the eighth postoperative day. Shoulder function was measured at the time of discharge and then at one and six months after surgery. Comparison of the two groups at six months revealed no difference in the duration and volume of wound drainage, wound complication rates or shoulder function. It is concluded that early or delayed shoulder exercise does not influence the outcome in terms of shoulder function in women after surgery for breast cancer. (Consumer Summary produced by Reliance Medical Information, Inc.)

The portal vein carries blood from the intestines directly to the liver, and in normal individuals this gives the liver first exposure to new substances entering the bloodstream. Unfortunately, metastatic tumor cells from colorectal cancer may also use this pathway to invade and colonize the liver. Patients undergoing surgery for primary colorectal cancer have a 25 percent chance of already having metastases in the liver, and autopsy of patients who have died of colorectal cancer reveals liver metastases between 50 and 80 percent of the time. Tumor cells may be surrounded by fibrin and platelets and may even form tiny 'tumor clots' which can bind to the lining of blood capillaries within the liver. A combination of antineoplastic agents may be infused directly into the portal vein to be carried rapidly to the liver; these include 5-fluorouracil, a chemotherapeutic agent that works against metastatic tumors, and heparin, an anticlotting agent that reduces the likelihood that fibrin-coated tumor cells in the circulation will attach in the liver. A total of 304 patients were included in a prospective randomized study; all patients had the primary colorectal cancer surgically removed. They were then divided into three treatment groups. One hundred and two patients had no further treatment after the surgery. Another ninety-nine patients received a portal vein infusion of the 5-fluorouracil and heparin combination under study, and an additional 103 patients received urokinase, which acts to break down fibrin clots. After a median follow-up of 44 months, 61 percent of the patients were disease-free; an additional 7 percent were alive but with recurrent disease. Compared to surgery only, the portal vein infusion of 5-fluorouracil and heparin reduced the risk of developing liver metastases by two-thirds; the data on the urokinase treatment indicated a reduction of the chance of liver metastases but this reduction was not statistically significant. The death rate in the 5-fluorouracil/heparin group was 75 percent of that in the surgery-only group, but this difference was not statistically significant. Although the data seem promising, the lack of statistical significance achieved in this study demands that a careful analysis of possible patient benefits be made before intraportal infusion of chemotherapeutic drugs can be recommended for patients with colorectal cancer. (Consumer Summary produced by Reliance Medical Information, Inc.)

Mutations in CCAAT/enhancer binding protein α (CEBPA) are seen in 5% to 14% of acute myeloid leukemia (AML) and have been associated with a favorable clinical outcome. Most AMLs with CEBPAmutations simultaneously carry 2 mutations (CEBPAdouble-mut), usually biallelic, whereas single heterozygous mutations (CEBPAsingle-mut) are less frequently seen. Using denaturing high-performance liquid chromatography and nucleotide sequencing, we identified among a cohort of 598 newly diagnosed AMLs a subset of 41 CEBPAmutant cases (28 CEBPAdouble-mutand 13 CEBPAsingle-mutcases). CEBPAdouble-mutassociated with a unique gene expression profile as well as favorable overall and event-free survival, retained in multivariable analysis that included cytogenetic risk, FLT3-ITD and NPM1mutation, white blood cell count, and age. In contrast, CEBPAsingle-mutAMLs did not express a discriminating signature and could not be distinguished from wild-type cases as regards clinical outcome. These results demonstrate significant underlying heterogeneity within CEBPAmutation-positive AML with prognostic relevance.

We evaluated the role of rituximab during remission induction chemotherapy in relapsed aggressive CD20+non-Hodgkin lymphoma. Of 239 patients, 225 were evaluable for analysis. Randomized to DHAP (cisplatin-cytarabine-dexamethasone)-VIM (etoposide-ifosfamide-methotrexate)-DHAP (cisplatin-cytarabine-dexamethasone) chemotherapy with rituximab (R; R-DHAP arm) were 119 patients (113 evaluable) and to chemotherapy without rituximab (DHAP arm) 120 patients (112 evaluable). Patients in complete remission (CR) and partial remission (PR) after 2 chemotherapy courses were eligible for autologous stem-cell transplantation. After the second chemotherapy cycle, 75% of the patients in the R-DHAP arm had responsive disease (CR or PR) versus 54% in the DHAP arm (P= .01). With a median follow-up of 24 months, there was a significant difference in failure-free survival (FFS24; 50% vs 24% vs, P< .001), and progression free survival (PFS24; 52% vs 31% P< .002) in favor of the R-DHAP arm. Cox-regression analysis demonstrated a significant effect of rituximab treatment on FFS24(HR 0.41, 95% confidence interval [CI] 0.29-0.57 versus 0.51, 95% CI 0.37-0.70) and overall-survival (OS24: HR 0.60 [0.41-0.89] vs 0.76 [0.52-1.10]) when adjusted for time since upfront treatment, age, World Health Organization performance status, and secondary age-adjusted international prognostic index. These results demonstrate improved FFS and PFS for relapsed aggressive B-cell NHL if rituximab is added to the re-induction chemotherapy regimen.