Systematic review and consensus definitions for standardised endpoints in perioperative medicine: postoperative cancer outcomes.

BACKGROUND: The Standardising Endpoints for Perioperative Medicine group was established to derive an appropriate set of endpoints for use in clinical trials related to anaesthesia and perioperative medicine. Anaesthetic or analgesic technique during cancer surgery with curative intent may influence the risk of recurrence or metastasis. However, given the current equipoise in the existing literature, prospective, randomised, controlled trials are necessary to test this hypothesis. As such, a cancer subgroup was formed to derive endpoints related to research in onco-anaesthesia based on a current evidence base, international consensus and expert guidance. METHODS: We undertook a systematic review to identify measures of oncological outcome used in the oncological, surgical, and wider literature. A multiround Delphi consensus process that included up to 89 clinician-researchers was then used to refine a recommended list of endpoints. RESULTS: We identified 90 studies in a literature search, which were the basis for a preliminary list of nine outcome measures and their definitions. A further two were added during the Delphi process. Response rates for Delphi rounds one, two, and three were 88% (n=9), 82% (n=73), and 100% (n=10), respectively. A final list of 10 defined endpoints was refined and developed, of which six secured approval by ≥70% of the group: cancer health related quality of life, days alive and out of hospital at 90 days, time to tumour progression, disease-free survival, cancer-specific survival, and overall survival (and 5-yr overall survival). CONCLUSION: Standardised endpoints in clinical outcomes studies will support benchmarking and pooling (meta-analysis) of trials. It is therefore recommended that one or more of these consensus-derived endpoints should be considered for inclusion in clinical trials evaluating a causal effect of anaesthesia-analgesia technique on oncological outcomes.

Effect of perioperative lidocaine on metastasis after sevoflurane or ketamine-xylazine anaesthesia for breast tumour resection in a murine model.

BACKGROUND: Breast cancer accounts for 7% of female cancer deaths, usually attributable to metastasis. While surgery is a mainstay of treatment, perioperative interventions may influence risk of metastasis during breast tumour resection. Amide local anaesthetics influence cancer cell biology via numerous mechanisms in vitro, but in vivo data is lacking. We aimed to test the hypothesis that perioperative lidocaine reduces pulmonary metastasis after inhalation and i.v. anaesthesia in the 4T1 murine breast cancer model. METHODS: 4T1 Cancer cells were injected into the mammary fat-pad of immunocompetent BALB/c female mice. After 7 days, the resultant tumour was excised under either sevoflurane or ketamine/xylazine anaesthesia with or without perioperative i.v. lidocaine (1.5 mg kg-1 bolus followed by 25 min infusion 2 mg kg-1 h-1). Fourteen days post-surgery, posthumous lung and liver specimens were examined for metastasis. Pro-inflammatory and pro-metastatic cytokines were profiled in post-mortem serum from a small number of the mice. RESULTS: Primary tumour diameter was similar between groups. Lidocaine reduced lung metastatic colony count vs sevoflurane alone; median (inter-quartile range) 0 (0-2) compared with 22.5 (0-481), P=0.02 and reduced the proportion of animals with pulmonary metastasis (28.5% compared with 52.5%, P=0.04). In mice receiving ketamine-xylazine, lidocaine did not decrease the overall colony count: 60 (26-123) compared with 23.5 (0-225), P=0.43, but increased the proportion of animals with pulmonary metastasis (100% compared with 50%, P<0.01). Post-mortem serum analysis demonstrated reduced pro-inflammatory and angiogenic cytokine expression in animals without metastasis which received lidocaine with sevoflurane. CONCLUSIONS: In this 4T1 murine model of breast cancer, lidocaine decreased pulmonary metastasis when combined with sevoflurane anaesthesia, perhaps via anti-inflammatory and anti-angiogenic effects. It had no such effect in mice given ketamine anaesthesia.

Low maternal serum unconjugated estriol during prenatal screening as an indication of placental steroid sulfatase deficiency and X-linked ichthyosis.

Placental sulfatase deficiency is an X-linked metabolic defect that occurs in about 1 in 2,000 to 5,000 males. It is associated with congenital ichthyosis. In this report, the authors document a case of placental sulfatase deficiency detected during routine prenatal screening of maternal serum by the triple test: serum alpha-fetoprotein (AFP), unconjugated estriol (uE3), and human chorionic gonadotropin (hCG). At 16-weeks gestation, her AFP was 20.9 IU/mL (multiple of the median [MOM] 0.83), hCG was 14.4 mIU/L (MOM 0.42) and her uE3 was 0.01 nmol/L (MOM 0.01). The extremely low uE3 indicated a possible placental sulfatase deficiency, congenital adrenal hypoplasia, or other unknown abnormality. On receiving this information, the obstetrician obtained a family history that was consistent with ichthyosis in the maternal grandfather and his siblings. Biochemical analysis of placenta documented the lack of sulfatase activity. This case illustrates that an extremely low level of maternal uE3 should prompt investigation of the family for evidence of X-linked ichthyosis associated with placental sulfatase deficiency.

Genetic parameter estimates of ultrasound-measured longissimus muscle area and 12th rib fat thickness in Brangus cattle.

Data from 2,101 Brangus calves born from 1986 to 1990 were analyzed with a REML procedure using a derivative-free algorithm in a mixed linear animal model to obtain variance component estimates of ultrasound-measured longissimus muscle area and fat thickness. Direct additive heritabilities (ha2) of .39 and .40 were obtained for age-constant weaning and yearling longissimus muscle area (WLMA and YLMA, respectively), with a genetic correlation (rg) of .66 between them. The rg of YLMA with birth weight (BWT), weaning weight (WWT), postweaning gain (PWG), yearling weight (YWT), frame score (FS), and scrotal circumference (SC) were .17, .29, .43, .38, .01, and .19, respectively. The ha2 of age-constant yearling 12th rib fat thickness (FAT) was .14, and cattle averaged .44 cm (SD = .19). Positive rg were obtained between FAT and WLMA (.19) and YLMA (.12). Negative rg of FAT with WWT, YWT, and SC were -.17, -.53, and -.33, respectively. Positive rg were obtained between FAT and BWT (.52), PWG (.44), and FS (.14). Maternal heritabilities (hm2) of WLMA, YLMA, and FAT were .01, .01, and .10, respectively. Weight-constant WLMA, YLMA, and FAT ha2 were .36, .39, and .11, respectively. Selection based on either age-constant YLMA or FAT could potentially result in 1.06 cm2 or .005 cm change per year, respectively, which would be slightly greater than change from selection based on weight-constant YLMA or FAT. Selection based on WLMA or YLMA should be effective, and changes in these traits, growth, and SC should be possible in tandem.(ABSTRACT TRUNCATED AT 250 WORDS)

Sonographic detection of monoamniotic twins.

The true incidence of monoamniotic twinning has been almost impossible to determine accurately because it requires closer inspection of the membranes and placenta at delivery than is usually performed. Sonography of 3440 patients presenting for genetic amniocentesis identified 39 twin gestations, one of which was monoamniotic (0.026%). Prospectively with ultrasound, four of the twin gestations had been thought to be monoamniotic. A more recent case of suspected monoamniotic twinning revealed two sacs when newer computer-based real-time equipment with variable focusing capability and improved spatial resolution was used. Sonographic diagnosis of monoamniotic twinning must be accurate since it identifies patients at higher risk for cord accidents. These patients need obstetrical care appropriate for a pregnancy at high risk. In addition, failure to identify a second sac that could harbor a chromosomally abnormal fetus has both medical and legal implications. State-of-the-art ultrasound equipment and attention to detail is required.

Intrapartum fetal heart rate patterns and neonatal intraventricular hemorrhage.

A goal for the obstetrician and neonatologist is to screen for risk factors associated with intraventricular hemorrhage (IVH) in the low-birthweight infant. Perinatal events that lead to neonatal metabolic and cardiovascular derangements seem to provoke IVH, and conflicting reports have implicated labor as being contributory. A fetal heart rate (FHR) abnormality during premature labor may be a predictor of subsequent neonatal IVH. For this reason, 5 years of FHR tracings at two university medical centers were reviewed for inborn infants who were delivered after premature labor and weighed less than or equal to 2000 gm. Sixty-four infants developed IVH, but pre-existing labor with a discernible FHR pattern was recorded in only 38 (59%) cases. Interpretations were reassuring in 17 (45%) cases, suspicious in 7 (18%) cases, and ominous in 14 (37%) cases. This proportion of FHR patterns was not significantly different from a matched group of premature infants without IVH during the same period. Interpretations of intrapartum FHR patterns of low-birthweight infants are limited, especially before 30 weeks gestation, and not useful in predicting neonatal IVH.

Comparison of the cellular cytotoxic activities of colostral lymphocytes and maternal peripheral blood lymphocytes.

Colostral lymphocytes (CL) from mothers 2 to 4 days post-partum and autologous maternal peripheral blood lymphocytes (PBL) were investigated for (1) natural killer (NK) and antibody-dependent cellular cytotoxic (ADCC) activities, (2) target binding ability, (3) interferon (IFN)- and interleukin 2 (IL2)-induced augmentation of NK activity, (4) lectin-dependent cellular cytotoxicity (LDCC), and (5) the ability of culture-derived soluble suppressor factor(s) to inhibit the NK activity of normal allogeneic lymphocytes. CL depleted of adherent cells and Percoll-separated NK-enriched subpopulations of CL demonstrated significantly lower NK and ADCC activities compared to autologous PBL. However, the target binding ability of CL was comparable to autologous PBL. Although the residual NK activity of CL was augmented by IFN and IL2, the activity was not enhanced to the same level shown by autologous PBL. CL also demonstrated a significant enhancement of LDCC activity, although the activity was not stimulated to the levels shown by PBL. Culture supernates of CL manifested greater suppression of the NK ability of allogeneic PBL than culture supernates produced by autologous PBL. These results are consistent with a model that suggests differential partitioning of lymphocyte subpopulations between colostrum and peripheral blood.