Perioperative administration of propranolol to women undergoing ovarian cancer surgery: A pilot study.
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ABSTRACT: Objective
This study was done to evaluate whether perioperative propranolol (ß-blocker) in ovarian cancer patients undergoing debulking surgery reduced perioperative tumor growth induced by surgical stress.Methods
This was a prospective randomized single institution analysis. The primary objective was to compare the changes in CA 125 level (changes between preoperation day 2 and postoperative day 7). As a study arm, patients received a low dose of propranolol 40 mg/day (4×10 mg) starting two days before surgery and 40 mg twice daily for three days following surgery.Results
Twenty-two patients were enrolled and 16 were evaluable for efficacy. The drug was well tolerated. The mean decrease of CA 125 during the seven perioperative days was 83.1±8.9% in the propranolol group and 72.4±14.7% in the placebo group. The difference was statistically significant (P=0.044). The change of C-reactive protein, cortisol, and anxiety score (State-Trait Anxiety Inventory-X1) were not different between the two groups.Conclusion
This preliminary result is the first to directly test the role of perioperative propranolol on tumor growth. Even with the small sample size and short term use of the drug, perioperative propranolol was effective in reducing tumor burden (as measured by CA 125) suggesting its potential benefits in decreasing perioperative tumor growth.
SUBMITTER: Jang HI
PROVIDER: S-EPMC5364099 | biostudies-literature | 2017 Mar
REPOSITORIES: biostudies-literature
Publications
Perioperative administration of propranolol to women undergoing ovarian cancer surgery: A pilot study.
Jang Hye-In HI Lim Soo-Hyun SH Lee Yoo-Young YY Kim Tae-Joong TJ Choi Chel Hun CH Lee Jeong-Won JW Kim Byoung-Gie BG Bae Duk-Soo DS
Obstetrics & gynecology science 20170316 2
<h4>Objective</h4>This study was done to evaluate whether perioperative propranolol (ß-blocker) in ovarian cancer patients undergoing debulking surgery reduced perioperative tumor growth induced by surgical stress.<h4>Methods</h4>This was a prospective randomized single institution analysis. The primary objective was to compare the changes in CA 125 level (changes between preoperation day 2 and postoperative day 7). As a study arm, patients received a low dose of propranolol 40 mg/day (4×10 mg) ...[more]
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Project description:BackgroundWomen with ovarian cancer have been shown to be at significant risk of malnutrition with incidence rates described as being between 28% to 67%. Nutrition interventions may improve clinical outcomes positively, nutritional status or quality of life measures in this patient group.ObjectivesThis review was conducted to assess the effects of nutrition interventions during the perioperative period for women with ovarian cancer.Search methodsElectronic searches were conducted of the Cochrane Gynaecological Cancer Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL 2012, Issue 7), Medline (1946 to July week 4 2012), Embase (1980 to 2012 week 31), DARE (to 7th August 2012) AMED (1985 to April 2012), BNI (1992 to April 2012), CINAHL (to April 2012). We also searched trials databases, conference proceedings and related citation lists. Reference listings were handsearched. No restrictions were applied on language or date.Selection criteriaRandomised controlled trials (RCTs) in which women 18 years and over with any stage of ovarian cancer, including recurrent cancer, were in the perioperative phase of treatment and received any type of nutrition intervention.Data collection and analysisTitles and abstracts were screened by two review authors with study selection discussed by a team. Pairs of review authors worked independently on data collection and compared findings.Main resultsA total of 4092 titles were screened and 14 full text reports reviewed; a single small study met the inclusion criteria. In the included RCT, 40 women (35 with ovarian cancer) had extensive elective surgery including bowel resection for treatment of gynaecological malignancy. Randomisation was made to either early oral feeding (oral fluids in the first 24 hours, solid foods on the following day) or to a 'traditional' feeding regimen where oral fluids and foods were delayed until there was evidence of bowel function. Most women in the early feeding group (14/18) were able to resume eating solid food one day after surgery. This resulted in a significantly shorter hospital stay with no increase in postoperative complications or change in quality of life measures in comparison with the women on the 'traditional' feeding regimen. The incidence of nausea and vomiting during the postoperative stay was similar in both groups and was noted in slightly more than half of the women. Overall survival was evaluated until 30 days following discharge from hospital; in this period, there was one death of a woman who had been in the 'traditional oral feeding' group, cause of death was not noted. We assessed risk of bias and found no high risk of bias was identified in the methodology and reporting of the included study, although there was an increased risk of bias due to the small size of the study in which not all of the women had ovarian cancer.Authors' conclusionsAlthough women with ovarian cancer have been shown to be at risk of malnutrition, there is a lack of evidence derived from RCTs evaluating the identification, assessment and treatment of malnutrition during the perioperative phase of treatment. There is evidence from one small study that some women with ovarian cancer undergoing surgery with associated bowel resection may safely commence oral fluids within 24 hours of surgery and solid foods on the following day. Further research is required, including a RCT, to generate guidance concerning the treatment of malnutrition in this patient group.
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Project description:BackgroundTissue injury induces inflammation and the surgical stress response, which are thought to be central to the orchestration of recovery or deterioration after surgery. Enhanced formation of reactive oxygen and nitrogen species accompanies the inflammatory response and triggers separate but integrated reduction/oxidation (redox) pathways that lead to oxidative and/or nitrosative stress (ONS). Quantitative information on ONS in the perioperative period is scarce. This single-centre exploratory study investigated the effects of major surgery on ONS and systemic redox status and their potential associations with postoperative morbidity.MethodsBlood was collected from 56 patients at baseline, end of surgery (EoS) and the first postoperative day (day-1). Postoperative morbidity was recorded using the Clavien-Dindo classification and further categorised into minor, moderate and severe. Plasma/serum measures included markers of lipid oxidation (thiobarbituric acid-reactive substances; TBARS, 4-hydroxynonenal; 4-HNE, 8-iso-prostaglandin F2⍺; 8-isoprostanes). Total reducing capacity was measured using total free thiols (TFTs) and ferric-reducing ability of plasma (FRAP). Nitric oxide (NO) formation/metabolism was measured using cyclic guanosine monophosphate (cGMP), nitrite, nitrate and total nitroso-species (RxNO). Interleukin-6 (IL-6) and tumour necrosis factor alpha (TNF-⍺) were measured to evaluate inflammation.ResultsBoth oxidative stress (TBARS) and nitrosative stress (total nitroso-species) increased from baseline to EoS (+14%, P = 0.003 and +138%, P < 0.001, respectively), along with an increase in overall reducing capacity (+9%, P = 0.03) at EoS and protein-adjusted total free thiols (+12%, P = 0.001) at day-1 after surgery. Nitrite, nitrate and cGMP concentrations declined concomitantly from baseline to day-1. Baseline nitrate was 60% higher in the minor morbidity group compared to severe (P = 0.003). The increase in intraoperative TBARS was greater in severe compared to minor morbidity (P = 0.01). The decline in intraoperative nitrate was more marked in the minor morbidity group compared to severe (P < 0.001), whereas the cGMP decline was greatest in the severe morbidity group (P = 0.006).ConclusionIn patients undergoing major HPB surgery, intraoperative oxidative and nitrosative stress increased, with a concomitant increase in reductive capacity. Baseline nitrate was inversely associated with postoperative morbidity, and the hallmarks of poor postoperative outcome include changes in both oxidative stress and NO metabolism.
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