Associations of accumulated persistent organic pollutants in breast adipose tissue with the evolution of breast cancer after surgery.

Chronic exposure to persistent organic pollutants (POPs) is suspected to contribute to the onset of breast cancer, but the impact on the evolution of patients after diagnosis is unclear. We aimed to analyze the contribution of long-term exposure to five POPs to overall mortality, cancer recurrence, metastasis, and development of second primary tumors over a global follow-up of 10 years after surgery in breast cancer patients in a cohort study. Between 2012 and 2014, a total of 112 newly diagnosed breast cancer patients were recruited from a public hospital in Granada, Southern Spain. Historical exposure to POPs was estimated by analyzing their concentrations in breast adipose tissue samples. Sociodemographic data were collected through face-to-face interviews, while data on evolution tumor were retrieved from clinical records. Statistical analyses were performed using Cox regression (overall survival, breast cancer recurrence or metastasis) and binary logistic regression models (joint outcome variable). We also tested for statistical interactions of POPs with age, residence, and prognostic markers. The third vs first tertile of hexachlorobenzene concentrations was associated with a lower risk of all-cause mortality (Hazard Ratio, HR = 0.26; 95 % Confidence Interval, CI = 0.07-0.92) and of the appearance of any of the four events (Odds Ratio = 0.37; 95 % CI = 0.14-1.03). Polychlorinated biphenyl 138 concentrations were significantly and inversely associated with risk of metastasis (HR = 0.65; 95 % CI = 0.44-0.97) and tumor recurrence (HR = 0.69; 95 % CI = 0.49-0.98). Additionally, p,p'-dichlorodiphenyldichloroethylene showed inverse associations with risk of metastasis in women with ER-positive tumors (HR = 0.49; 95 % CI = 0.25-0.93) and in those with a tumor size <2.0 cm (HR = 0.39; 95 % CI = 0.18-0.87). The observed paradoxical inverse associations of POP exposure with breast cancer evolution might be related to either a better prognosis of hormone-dependent tumors, which have an approachable pharmacological target, or an effect of sequestration of circulating POPs by adipose tissue.

Associations of persistent organic pollutants in serum and adipose tissue with breast cancer prognostic markers.

This study aimed to evaluate associations between exposure to a group of persistent organic pollutants, measured in both adipose tissue and serum samples from breast cancer patients, and a set of tumor prognostic markers. The study population comprised 103 breast cancer patients recruited in Granada, Southern Spain. Data for tumor prognostic markers were retrieved from hospital clinical records and socio-demographic information was gathered by questionnaire. Persistent organic pollutants were quantified by gas chromatography with electron capture detection. Exposure levels were categorized in quartiles, and associations were evaluated using unconditional logistic regression. Adipose tissue HCB concentrations were associated positively with ER and PR expression (p-trends=0.044 and 0.005, respectively) and negatively with E-Cadherin and p53 expression (p-trends=0.012 and 0.027, respectively). PCB-180 adipose tissue concentrations were positively associated with HER2 expression (p-trend=0.036). Serum PCB-138 concentrations were positively associated with ER and PR expression (p-trends=0.052 and 0.042, respectively). The risk of p53 expression was higher among women in the lowest quartile of serum PCB-138 concentrations, but no significant trend was observed (p-trend=0.161). These findings indicate that human exposure to certain persistent organic pollutants might be related to breast cancer aggressiveness. We also highlight the influence on exposure assessment of the biological matrix selected, given that both serum and adipose tissue might yield relevant information on breast cancer prognosis.

Comparative study of intubating conditions at the first minute with suxamethonium, rocuronium and different priming techniques of rocuronium.

BACKGROUND AND OBJECTIVE: To evaluate orotracheal intubation conditions after 1 min. PATIENTS AND METHODS: A prospective randomized study with 376 adult American Society of Anesthesiologists (ASA) Grade I-III patients. Each patient received propofol, fentanyl and either suxamethonium (1 mg kg(-1)) or rocuronium. The intubating dose of rocuronium (2 x ED95) was preceded 4 min earlier by saline, or a 0.1 x ED95 priming dose of rocuronium, atracurium, cis-atracurium, vecuronium or mivacurium. Intubating conditions were graded as excellent, good or poor with respect to laryngoscopy, vocal cord position and movement and reaction to intubation and/or cuff inflation. RESULTS: There were significant differences (P < 0.05) in laryngoscopy between suxamethonium and rocuronium primed with saline, atracurium or cis-atracurium. With respect to vocal cord position and movement during intubation, rocuronium without priming differed significantly from all other groups and for reaction to insertion of tracheal tube and/or cuff inflation. Rocuronium without priming differed significantly from all other groups except for rocuronium primed with itself. The mivacurium group showed more signs of pre-curarization than other groups (P < 0.05). There were significant differences between rocuronium alone and the other groups when final intubating conditions were compared. CONCLUSIONS: Priming rocuronium with 0.1 x ED95 of vecuronium, rocuronium, atracurium or cis-atracurium is a safe technique and did not increase risk of pre-curarization in healthy patients.

Cost-effectiveness of three combinations of antiemetics in the prevention of postoperative nausea and vomiting.

BACKGROUND: This study compares the cost-effectiveness of three combinations of antiemetics in the prevention of postoperative nausea and vomiting (PONV). METHODS: We conducted a prospective, double-blind study. Ninety ASA I-II females, 18-65 yr, undergoing general anaesthesia for major gynaecological surgery, with standardized postoperative analgesia (intrathecal 0.2 mg plus i.v. PCA morphine), were randomly assigned to receive: ondansetron 4 mg plus droperidol 1.25 mg after induction and droperidol 1.25 mg 12 h later (Group 1); dexamethasone 8 mg plus droperidol 1.25 mg after induction and droperidol 1.25 mg 12 h later (Group 2); ondansetron 4 mg plus dexamethasone 8 mg after induction and placebo 12 h later (Group 3). A decision analysis tree was used to divide each group into nine mutually exclusive subgroups, depending on the incidence of PONV, need for rescue therapy, side effects and their treatment. Direct cost and probabilities were calculated for each subgroup, then a cost-effectiveness analysis was conducted from the hospital point of view. RESULTS: Groups 1 and 3 were more effective (80 and 70%) than Group 2 (40%, P=0.004) in preventing PONV but also more expensive. Compared with Group 2, the incremental cost per extra patient without PONV was euro;6.99 (95% CI, -1.26 to 36.57) for Group 1 and euro;13.55 (95% CI, 0.89-132.90) for Group 3. CONCLUSION: Ondansetron+droperidol is cheaper and at least as effective as ondansetron+ dexamethasone, and it is more effective than dexamethasone+droperidol with a reasonable extra cost.

A comparison of three antiemetic combinations for the prevention of postoperative nausea and vomiting.

UNLABELLED: In this study we compared the efficacy and safety of three antiemetic combinations in the prevention of postoperative nausea and vomiting (PONV). Ninety ASA status I-II women, aged 18-65 yr, undergoing general anesthesia for major gynecological surgery, were included in a prospective, randomized, double-blinded study. A standardized anesthetic technique and postoperative analgesia (intrathecal morphine plus IV patient-controlled analgesia (PCA) with morphine) were used in all patients. Patients were randomly assigned to receive ondansetron 4 mg plus droperidol 1.25 mg after the induction of anesthesia and droperidol 1.25 mg 12 h later (Group 1, n = 30), dexamethasone 8 mg plus droperidol 1.25 mg after the induction of anesthesia and droperidol 1.25 mg 12 h later (Group 2, n = 30), or ondansetron 4 mg plus dexamethasone 8 mg after the induction of anesthesia and placebo 12 h later (Group 3, n = 30). A complete response, defined as no PONV in 48 h, occurred in 80% of patients in Group 1, 70% in Group 3, and 40% in Group 2 (P = 0.004 versus Groups 1 and 3). The incidences of side effects and other variables that could modify the incidence of PONV were similar among groups. In conclusion, ondansetron, in combination with droperidol or dexamethasone, is more effective than dexamethasone in combination with droperidol in women undergoing general anesthesia for major gynecological surgery with intrathecal morphine plus IV PCA with morphine for postoperative analgesia. IMPLICATIONS: The combination of ondansetron plus dexamethasone or droperidol was significantly better than the combination of dexamethasone plus droperidol in the prophylaxis of postoperative nausea and vomiting in women undergoing general anesthesia for major gynecological surgery, with intrathecal and IV morphine (patient-controlled analgesia) for management of postoperative pain.

Detección precoz de la hiperpotasemia por reperfusión en el trasplante hepático mediante monitorización del bloqueo neuromuscular / Hyperkaliemia due to reperfusion during liver transplantation: early detection by monitoring meuromuscular blockade

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A comparative study with oral nifedipine, intravenous nimodipine, and magnesium sulfate in postoperative analgesia.

UNLABELLED: We tested the ability of two L-type calcium channel blockers (nifedipine and nimodipine) and the N-methyl D-aspartate natural antagonist magnesium to decrease morphine requirements and pain in the postoperative period in 92 patients undergoing elective colorectal surgery. In a randomized, double-blinded study, patients were assigned to one of four groups. The control group received placebo. The nifedipine group received 60 mg of oral nifedipine. The magnesium group received an initial dose of 30 mg/kg followed by 10 mg x kg(-1) x h(-1) of magnesium sulfate over 20 h. The nimodipine group received 30 microg x kg(-1) x h(-1) of nimodipine over 20 h. Postoperative morphine consumption was assessed for 48 h. Pain at rest and pain on movement were assessed up to the fifth day postsurgery. There were no differences among groups in postoperative morphine consumption at 12 and 24 h. The nifedipine group consumed more morphine than the control and nimodipine groups during 24-48 h. Pain at rest scores were higher at 16 and 24 h in the nifedipine group than in the other three groups. Pain on movement scores were lower at 72 h in the nimodipine group than in the control and nifedipine groups. In conclusion, the perioperative application of oral nifedipine, IV nimodipine, or IV magnesium sulfate failed to decrease postoperative morphine requirements after colorectal surgery. IMPLICATIONS: The increase of intracellular calcium plays a key role in spinal transmission of pain and in the establishment of central sensitization. We examined the effects of nifedipine, nimodipine, and magnesium sulfate in postoperative analgesia after colorectal surgery. We found no differences in morphine consumption with the administration of each drug alone.

[Cisatracurium]. / Cisatracurio.

Cisatracurium is one of ten isomers that form the racemic mix of atracurium (51W89 or 1 R-cis, 1'R-cis atracurium). It is three times more potent than atracurium itself and hemodynamically stable thanks to its scarce release of histamine. Cisatracurium is hydrolyzed mainly by the pathway of Hofmann (77%) and to a lesser degree it is metabolized by organ-dependent modes (mainly by the kidney (16%)). Dose therefore hardly needs to be changed for elderly patients or those with liver, kidney or cardiovascular disease. The calculated ED95 is 0.05 mg.kg-1 (0.04 mg.kg-1 in children), although a dose two to four times greater is used under clinical conditions to shorten tracheal intubation time because of low onset of blockade, particularly in comparison with rocuronium. The period of deep blockade (lack of response to neurostimulation) is prolonged by the higher dose, but recovery is dose-independent and recovery indices are similar. Cisatracurium has proven useful in intensive care because of its hemodynamic stability, which is comparable to that of steroid derivatives but with faster recovery from blockade once administration is discontinued. Its metabolism predominantly through Hofmann's pathway, with less laudanosine formation than is produced by atracurium, is also appreciated. Cisatracurium is described as the nondepolarizing muscle relaxant of choice for medium-to-long-term surgery on hemodynamically unstable patients or those with kidney or liver disease, and for neuromuscular blockade in intensive care.

[Mivacurium]. / Mivacurio.

Mivacurium is a short-acting nondepolarizing muscle relaxant (NDPMR) with a benzyl-isoquinoline structure and rapid, spontaneous reversal. It is hydrolyzed by cholinesterase in plasma and its chemical structure favors histamine release, leading to cutaneous or cardiovascular symptoms, particularly when the dose is increased or when the drug is injected rapidly. Both duration of effect and reversal of mivacurium are less dose dependent than they are with intermediate-duration NDPMRs. In adults the recommended dose for intubation (2 to 3 times the ED95) induces clinically effective blockade lasting 15 to 25 minutes, with spontaneous recovery occurring 10 to 20 minutes later. In children two to 12 years old given the same dose, duration of action is shorter and reversal occurs more rapidly. These properties reduce the likelihood of antagonizing the residual neuromuscular blockade. The duration of successive doses is similar and continuous infusion does not affect reversal. Neuromuscular blockade may be prolonged in patients with low plasma cholinesterase activity, particularly in individuals who are homozygous for the atypical plasma cholinesterase gene. Monitoring is therefore recommended when mivacurium is used. Provided patients have normal plasma cholinesterase activity, mivacurium is indicated for interventions that are short or of unpredictable duration when rapid reversal of neuromuscular blockade is required, or whenever anticholinesterase agents must be avoided.

Combination of ondansetron and droperidol in the prophylaxis of postoperative nausea and vomiting.

The aim of this study was to compare the efficacy and safety of ondansetron plus droperidol with each drug alone or placebo in the prevention of postoperative nausea and vomiting (PONV). One hundred females, aged 18-65 yr, ASA physical status I-II, undergoing general anesthesia for elective abdominal surgery were included in a prospective, double-blind, placebo-controlled, randomized study. A standardized anesthetic technique and postoperative analgesia (ketorolac plus patient-controlled analgesia [PCA] with morphine) were used in all patients. Patients were randomly assigned to receive placebo (Group 1, n = 25), droperidol 2.5 mg with induction of anesthesia and 1.25 mg 12 h later (Group 2, n = 25), ondansetron 4 mg with induction (Group 3, n = 25), and ondansetron plus droperidol at the same doses as Groups 3 and 2, respectively (Group 4, n = 25). A complete response, defined as no PONV in 48 h, occurred in 28% of patients in Group 1, 60% in Group 2 (P < 0.05 vs Group 1), 56% in Group 3 (P < 0.05 vs Group 1), and 92% in Group 4 (P < 0.01 vs Groups 1, 2, and 3). Sedation was significantly greater with droperidol (Groups 2 and 4) for 12 h postoperatively. In conclusion, the combination of ondansetron plus droperidol was more effective than each antiemetic alone or placebo in the prevention of PONV in women undergoing elective abdominal surgery.

Combination of ondansetron and dexamethasone in the prophylaxis of postoperative nausea and vomiting.

We studied 100 ASA I-II females undergoing general anaesthesia for major gynaecological surgery, in a prospective, double-blind, placebo-controlled, randomized study. Patients received one of four regimens for the prevention of postoperative nausea and vomiting (PONV): ondansetron 4 mg (n = 25), dexamethasone 8 mg (n = 25), ondansetron with dexamethasone (4 mg and 8 mg, respectively, n = 25) or placebo (saline, n = 25) There were no differences in background factors or factors related to operation and anaesthesia, morphine consumption, pain or side effects between groups. The incidence of nausea and emetic episodes in the ondansetron with dexamethasone group was lower than in the placebo (P < 0.01), ondansetron (P < 0.05) and dexamethasone (P = 0.057) groups. There were no differences between ondansetron and dexamethasone, and both were more effective than placebo (P < 0.05 and P < 0.01, respectively). Dexamethasone appeared to be preferable in preventing nausea than emetic episodes. Fewer patients in the ondansetron with dexamethasone group needed antimetic rescue (P < 0.01 vs placebo and P < 0.05 vs ondansetron). We conclude that prophylactic administration of combined ondansetron and dexamethasone is effective in preventing PONV.

[Reduction of the need for blood derivatives in liver transplantation using aprotinin]. / Reducción de los requerimientos de hemoderivados en el trasplante hepático con aprotinina.

OBJECTIVES: To evaluate the efficacy of aprotinin in reducing the need for blood products in orthotopic liver transplantation. PATIENTS AND METHODS: Blood product needs and coagulation test results were studied in 42 adults with cirrhosis of the liver who received orthotopic liver transplants. The first 16 liver transplants carried out without aprotinin (control group) were compared with the next 26 consecutive transplant patients who received aprotinin. Each of the first 9 received a loading dose of 2 million units that was followed by the infusion of half a million units per hour until the end of surgery. The next 17 received the same infusion dose at the same rate but no loading dose. RESULTS: Patients who received aprotinin required fewer transfusions of blood products (5.3 units of packed red blood cells as opposed to 13 units; 9 units of fresh frozen plasma versus 14.6 units; 1.7 units of platelets versus 4.2 units; and 3.8 units of cryoprecipitates versus 8.8 units). We observed a marked reduction of fibrinolysis (less increase in D dimers after removal of the liver when aprotinin was used. CONCLUSIONS: Prophylactic use of aprotinin during surgery has a beneficial effect on hemostatic mechanisms, reducing the need for blood products. A reduction in fibrinolysis seems to contribute to this effect.

[Does propofol have advantages over midazolam and isoflurane? Comparative study of 2 total intravenous anesthesia techniques using midazolam and propofol, versus balanced anesthesia with isoflurane]. / Tiene ventajas propofol sobre midazolam e isoflurano? Estudio comparativo de dos técnicas de anestesia total intravenosa con midazolam y propofol, y anestesia balanceada con isoflurano.

OBJECTIVES: To compare two techniques for total intravenous anesthesia (TIVA): midazolam-alfentanil-flumazenil and propofol-alfentanil, contrasting them with combined anesthesia (thiopental-isoflurane-alfentanil) and assessing the efficacy of flumazenil in continuous perfusion for preventing resedation in TIVA with midazolam. PATIENTS AND METHODS: The efficacy and clinical tolerance of the 3 anesthetic techniques with propofol, midazolam or isoflurane were studied in 63 patients undergoing elective breast, lumbar or gynecological surgery. Anesthetic induction was achieved with midazolam 0.3 mg/kg-1 (group M), propofol 2.5 mg/kg-1 (group P) or thiopental 3 mg/kg-1 (group I); all patients also received 50 micrograms/kg-1 alfentanil and vecuronium bromide 0.12 mg/kg-1/h-1. Maintenance was achieved with midazolam in perfusion at 0.12 mg/kg-1/h-1 (group M); propofol in perfusion at 7 mg/kg-1/h-1 and a pre-incision dose of 1.5 mg/kg-1 (group P); and isoflurane at 1.15% (group I). The 3 groups also received one pre-incision dose of alfentanil 25 micrograms/kg-1 and post-incision perfusion at 60 micrograms/kg-1/h-1. The infusion of alfentanil was changed by amounts of 20 micrograms/kg-1/h-1 in accordance with the patient's response to surgery. After surgery patients in group M received flumazenil 0.5 mg i.v. over 30 sec and a perfusion of flumazenil 0.5 mg over 60 min. Parameters indicating efficacy were: 1) total dose and timing of alfentanil; 2) number of instances of inadequate anesthesia; 3) peri-operative amnesia; 4) times of awakening and extubation after surgery, and 5) the number of patients in each group who required naloxone. Parameters indicating tolerance were: 1) hemodynamic variables; 2) the number of postoperative desaturations; 3) level of sedation, comprehension and motor coordination and orientation; 4) the "G/g detection" test and the memory recall test; 5) adverse side effects; 6) need for postoperative analgesia, and 7) evaluation of the anesthetic technique. RESULTS: The 3 techniques afforded effective control of hemodynamic response to intubation and surgical incision. Anesthetic maintenance was easy and safe with isoflurane and propofol. Higher doses of alfentanil, however, were needed with midazolam and we found a higher incidence of signs of superficial anesthesia. Reversion of midazolam with flumazenil 0.5 mg i.v. produced earlier awakening, although this was followed later by relapse into hypno-sedation that could not be prevented with a perfusion of flumazenil. Although recovery from anesthesia was slower with propofol than with isoflurane, we observed no differences in level of sedation, motor coordination and postoperative comprehension. Maintenance with isoflurane produced a higher incidence of adverse side effects such as tremors and nausea after surgery. CONCLUSIONS: None of the TIVA techniques proved superior in all the parameters studied during anesthetic maintenance when compared with balanced isoflurane-alfentanil, although the propofol-alfentanil combination was found to be superior to that of midazolam-alfentanil. After anesthesia, however, recovery was better with the association of propofol-alfentanil and adverse side effects were fewer. Flumazenil at the doses used was ineffective for preventing resedation due to midazolam.