Abstract Evidence suggests that perioperative allogeneic blood transfusion increases the risk of infectious complications after major surgery and of cancer recurrence after curative operation. This has been attributed to immuno-suppression. Several authors have suggested that filtered whole blood and/or red cell concentrate, or leucocyte-and buffy coat-reduced red cells in artificial medium or their own plasma, may reduce postoperative immuno-suppression. It was also anticipated that the use of autologous blood might minimize the risk of perioperative transfusion, but studies have unexpectedly shown similar postoperative infectious complications and cancer recurrence and/or survival rates in patients receiving autologous blood donated before operation and those receiving allogeneic blood. Future studies should identify common risk factors associated with blood storage.
Updated National Academy of Clinical Biochemistry (NACB) Laboratory Medicine Practice Guidelines for the use of tumor markers in the clinic have been developed.Published reports relevant to use of tumor markers for 5 cancer sites--testicular, prostate, colorectal, breast, and ovarian--were critically reviewed.For testicular cancer, alpha-fetoprotein, human chorionic gonadotropin, and lactate dehydrogenase are recommended for diagnosis/case finding, staging, prognosis determination, recurrence detection, and therapy monitoring. alpha-Fetoprotein is also recommended for differential diagnosis of nonseminomatous and seminomatous germ cell tumors. Prostate-specific antigen (PSA) is not recommended for prostate cancer screening, but may be used for detecting disease recurrence and monitoring therapy. Free PSA measurement data are useful for distinguishing malignant from benign prostatic disease when total PSA is <10 microg/L. In colorectal cancer, carcinoembryonic antigen is recommended (with some caveats) for prognosis determination, postoperative surveillance, and therapy monitoring in advanced disease. Fecal occult blood testing may be used for screening asymptomatic adults 50 years or older. For breast cancer, estrogen and progesterone receptors are mandatory for predicting response to hormone therapy, human epidermal growth factor receptor-2 measurement is mandatory for predicting response to trastuzumab, and urokinase plasminogen activator/plasminogen activator inhibitor 1 may be used for determining prognosis in lymph node-negative patients. CA15-3/BR27-29 or carcinoembryonic antigen may be used for therapy monitoring in advanced disease. CA125 is recommended (with transvaginal ultrasound) for early detection of ovarian cancer in women at high risk for this disease. CA125 is also recommended for differential diagnosis of suspicious pelvic masses in postmenopausal women, as well as for detection of recurrence, monitoring of therapy, and determination of prognosis in women with ovarian cancer.Implementation of these recommendations should encourage optimal use of tumor markers.
The levels of cysteine proteinase inhibitors stefin A, stefin B, and cystatin C were determined using ELISAs in sera obtained preoperatively from 345 patients with colorectal cancer and in control sera from 125 healthy blood donors. The levels of stefin A and cystatin C were found to be moderately increased in patient sera (1.4-fold and 1.6-fold, respectively; P < 0.0001), whereas the level of stefin B remained statistically unchanged when compared with controls. The medians were 4.3 ng/ml versus 3.2 ng/ml for stefin A, 1.2 ng/ml versus 1.7 ng/ml for stefin B, and 679 ng/ml versus 425 ng/ml for cystatin C. In patient sera, a weak correlation of cystatin C with age (r = 0.34; P < 0.001) and gender (P = 0.01) was found. Stefin A and cystatin C levels were independent of Dukes' stage, whereas stefin B correlated significantly with Dukes' stage, its level being the highest in stage D (P < 0.007). Stefin B and cystatin C correlated with survival, whereas stefin A was not a significant prognostic factor in this study. Using medians as cutoff values, patients with high levels of stefin B and patients with high levels of cystatin C exhibited a significantly higher risk of death than those with low levels of inhibitors (hazard ratio = 1.6; 95% confidence interval, 1.2-2.2; P = 0.002 for stefin B; hazard ratio = 1.3; 95% confidence interval, 1.0-1.8; P = 0.04 for cystatin C). Our results reveal a correlation between high levels of extracellular cysteine proteinase inhibitors and short survival in patients with colorectal cancer, and the data thus support previous studies suggesting a contributing role of protease inhibitors in the progression of cancer.
Abstract Objective Pre‐ and post‐operative plasma tissue inhibitor of metalloproteinases‐1 (TIMP‐1) levels have a prognostic impact on patients with colorectal cancer. However, the surgical trauma may play an essential role in regulation of plasma TIMP‐1 levels, which in turn may influence subsequent TIMP‐1 measurements. Patients and methods Consecutively, 48 patients with colon cancer (CC) and 12 patients with nonmalignant colonic disease were randomised to undergo elective laparoscopically assisted or open resection followed by fast track recovery. Plasma samples were collected just before and 1, 2 and 6 h after skin incision, and 1, 2, 8 and 30 days after surgery. TIMP‐1 was determined concurrently in all samples by a validated ELISA method. Results Geometric mean preoperative TIMP‐1 level was 142 ng/ml (range 54–559 ng/ml) among CC patients compared with 106 ng/ml (range 64–167 ng/ml) among patients with nonmalignant diseases ( P < 0.0001). TIMP‐1 levels were decreased significantly 2 h after skin incision compared to the preoperative levels returning to preoperative levels at 6 h. A highly significant ( P < 0.0001) maximum level was observed 1 day after surgery and was decreasing to preoperative levels 30 days after surgery. Patients undergoing laparoscopically assisted or open resection had similar TIMP‐1 levels at each time point. Conclusions Major surgery has considerable impact on plasma TIMP‐1 levels. Intra‐ and post‐operative changes of plasma TIMP‐1 levels are independent of the surgical approach, and resection for CC does not lead to a significant decrease of plasma TIMP‐1 levels within 30 days postoperatively.
The release of superoxide anion from blood monocytes was studied in eight patients with acute primary attack P. falciparum malaria. Before treatment a significant enhancement of the oxidative burst prevailed, which contrasts with previous findings of a depressed monocyte chemotactic responsiveness. During treatment and after clinical recovery the activity of superoxide anion release normalized in all patients.