Analgesia for major laparoscopic abdominal surgery: a randomised feasibility trial using intrathecal morphine.

Effective pain control enhances patient recovery after surgery. Laparoscopic techniques for major abdominal surgery are increasingly utilised to reduce surgical trauma. Intrathecal morphine is an attractive analgesic option that is gaining popularity. However, limited evidence guides its use in the setting of laparoscopic surgery. In addition, enhanced recovery after surgery pathways advocate opioid-sparing techniques. We conducted a feasibility trial to compare intrathecal morphine with non-neuraxial analgesia in laparoscopic or laparoscopic-assisted major abdominal surgery to inform the design of a future large clinical trial. This multicentre, double-blind, randomised controlled trial was conducted at two tertiary hospitals in Australia. Fifty-one patients were randomly allocated to receive either intrathecal morphine (intervention group) or a sham subcutaneous injection of normal saline in the lumbar area (control group) immediately before the induction of general anaesthesia. Co-primary outcomes were patient recruitment and successful adherence to treatment allocation as per the study protocol. The primary endpoints of feasibility and protocol adherence were met with a 46% recruitment rate (51 of 110 eligible patients) and 96% protocol adherence. There was only one patient with failed access to the intrathecal space. For secondary endpoints, fewer patients in the intrathecal morphine group required opioids in the post-anaesthesia care unit, their postoperative pain scores at rest were lower across the four time-points measured (p = 0.007), but not dynamic pain scores (p = 0.061), and pruritus was more common following intrathecal morphine (p = 0.007). Total oral morphine equivalents until postoperative day 3 were less in the intrathecal morphine group (median (95%CI) difference 82 (-13 to 168) mg), but this reduction was not statistically significant (p = 0.10). These findings support conducting a definitive clinical trial.

Organic food consumption and the incidence of cancer in a large prospective study of women in the United Kingdom.

BACKGROUND: Organically produced foods are less likely than conventionally produced foods to contain pesticide residues. METHODS: We examined the hypothesis that eating organic food may reduce the risk of soft tissue sarcoma, breast cancer, non-Hodgkin lymphoma and other common cancers in a large prospective study of 623 080 middle-aged UK women. Women reported their consumption of organic food and were followed for cancer incidence over the next 9.3 years. Cox regression models were used to estimate adjusted relative risks for cancer incidence by the reported frequency of consumption of organic foods. RESULTS: At baseline, 30%, 63% and 7% of women reported never, sometimes, or usually/always eating organic food, respectively. Consumption of organic food was not associated with a reduction in the incidence of all cancer (n=53 769 cases in total) (RR for usually/always vs never=1.03, 95% confidence interval (CI): 0.99-1.07), soft tissue sarcoma (RR=1.37, 95% CI: 0.82-2.27), or breast cancer (RR=1.09, 95% CI: 1.02-1.15), but was associated for non-Hodgkin lymphoma (RR=0.79, 95% CI: 0.65-0.96). CONCLUSIONS: In this large prospective study there was little or no decrease in the incidence of cancer associated with consumption of organic food, except possibly for non-Hodgkin lymphoma.

Body size in relation to incidence of subtypes of haematological malignancy in the prospective Million Women Study.

BACKGROUND: Greater adiposity and height have been associated with increased risk of haematological malignancies. Associations for disease subtypes are uncertain. METHODS: A cohort of 1.3 million middle-aged U.K. women was recruited in 1996-2001 and followed for 10 years on average. Potential risk factors were assessed by questionnaire. Death, emigration, and incident cancer were ascertained by linkage to national registers. Adjusted relative risks were estimated by Cox regression. RESULTS: During follow-up, 9162 participants were diagnosed with lymphatic or haematopoietic cancers. Each 10 kg m(-2) increase in body mass index was associated with relative risk of 1.20 (95% confidence interval: 1.13-1.28) for lymphoid and 1.37 (1.22-1.53) for myeloid malignancy (P=0.06 for heterogeneity); similarly, Hodgkin lymphoma 1.64 (1.21-2.21), diffuse large B-cell lymphoma 1.36 (1.17-1.58), plasma cell neoplasms 1.21 (1.06-1.39), acute myeloid leukaemia 1.47 (1.19-1.81), and myeloproliferative/myelodysplastic syndromes 1.32 (1.15-1.52). Each 10 cm increase in height was associated with relative risk of 1.21 (1.16-1.27) for lymphoid and 1.11 (1.02-1.21) for myeloid malignancy (P=0.07 for heterogeneity); similarly, mature T-cell malignancies 1.36 (1.03-1.79), diffuse large B-cell lymphoma 1.28 (1.14-1.43), follicular lymphoma 1.28 (1.13-1.44), plasma cell neoplasms 1.12 (1.01-1.24), chronic lymphocytic leukaemia/small lymphocytic lymphoma 1.23 (1.08-1.40), and acute myeloid leukaemia 1.22 (1.04-1.42). There was no significant heterogeneity between subtypes. CONCLUSION: In middle-aged women, greater body mass index and height were associated with modestly increased risks of many subtypes of haematological malignancy.

Reproductive factors and risk of oesophageal and gastric cancer in the Million Women Study cohort.

BACKGROUND: Hormonal factors may influence risk for upper gastrointestinal cancers in women. We examined risk of oesophageal and gastric cancers in relation to reproductive factors in a large UK cohort, the Million Women Study. METHODS: Among 1,319,409 women aged on average 56 years at recruitment, 1186 incident cancers of the oesophagus and 1194 of the stomach were registered during 11.9 million person-years' observation. Adjusted relative risks (RRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models. RESULTS: Risks of both oesophageal and gastric cancer were significantly higher in postmenopausal than in pre- or peri-menopausal women (RRs 1.46, 1.07-2.00 and 1.59, 1.15-2.20, respectively; P≤0.01 for both); and, among postmenopausal women, risk was higher the younger women were at menopause (RR, 95% CI per 5 years younger at menopause 1.18, 1.05-1.34 for oesophageal cancer and 1.18, 1.04-1.34 for stomach cancer, P(trend)=0.01 for both). For factors relating to childbearing, including women's age at first birth, their number of children, and breastfeeding history, the only significant association was a higher risk of oesophageal cancer in nulliparous, compared with parous, women (RR 1.31, 1.11-1.55; P=0.002). When risks for squamous cell and adenocarcinomas of the oesophagus were compared, most did not differ significantly, but statistical power was limited. CONCLUSION: Both oesophageal and gastric cancer risks appeared to be related to menopausal status and age at menopause, but there was little consistent evidence for associations with factors related to childbearing.

Alcohol drinking, tobacco smoking and subtypes of haematological malignancy in the UK Million Women Study.

BACKGROUND: Previous research suggests associations of lower alcohol intake and higher tobacco consumption with increased risks of haematological malignancy. The prospective Million Women Study provides sufficient power for reliable estimates of subtype-specific associations in women. METHODS: Approximately 1.3 million middle-aged women were recruited in the United Kingdom during 1996-2001 and followed for death, emigration and cancer registration until 2009 (mean 10.3 years per woman); potential risk factors were assessed by questionnaire. Adjusted relative risks were estimated by Cox regression. RESULTS: During follow-up, 9162 incident cases of haematological malignancy were recorded, including 7047 lymphoid and 2072 myeloid cancers. Among predominantly moderate alcohol drinkers, higher intake was associated with lower risk of lymphoid malignancies, in particular diffuse large B-cell lymphoma (relative risk 0.85 per 10 g alcohol per day (95% confidence interval 0.75-0.96)), follicular lymphoma (0.86 (0.76-0.98)) and plasma cell neoplasms (0.86 (0.77-0.96)). Among never- and current smokers, higher cigarette consumption was associated with increased risk of Hodgkin lymphoma (1.45 per 10 cigarettes per day (1.22-1.72)), mature T-cell malignancies (1.38 (1.10-1.73)) and myeloproliferative/myelodysplastic disease (1.42 (1.31-1.55)). CONCLUSION: These findings confirm and extend existing evidence for associations of subtypes of haematological malignancy with two common exposures in women.

Cigarette smoking and risk of acoustic neuromas and pituitary tumours in the Million Women Study.

BACKGROUND: The relationship between cigarette smoking and incidence of acoustic neuromas and pituitary tumours is uncertain. METHODS: We examined the relation between smoking and risk of acoustic neuromas and pituitary tumours in a prospective study of 1.2 million middle-aged women in the United Kingdom. RESULTS: Over 10.2 million person years of follow-up, 177 women were diagnosed with acoustic neuromas and 174 with pituitary tumours. Current smokers at recruitment were at significantly reduced risk of incident acoustic neuroma compared with never smokers (adjusted relative risk (RR)=0.41, 95% confidence interval (CI)=0.24-0.70, P=0.001). Past smokers did not have significantly different risk of acoustic neuroma than never smokers (RR=0.87, 95% CI=0.62-1.22, P=0.4). Smoking was not associated with incidence of pituitary tumours (RR in current vs never smokers=0.91, 95% CI=0.60-1.40, P=0.7). CONCLUSION: Women who smoke are at a significantly reduced risk of acoustic neuromas, but not of pituitary tumours, compared with never smokers. Acoustic neuromas are much rarer than the cancers that are increased among smokers.

Reproductive factors and specific histological types of breast cancer: prospective study and meta-analysis.

Little is known about how reproductive factors affect the risk of breast cancers of different histology. In an analysis of prospective data on 1.2 million middle-aged UK women, we used proportional hazards models to estimate the relative risks of six histological types in relation to menarche, childbearing and menopause. During 8.7 million person-years of follow-up, 17 923 ductal, 3332 lobular, 1062 tubular, 944 mixed ductal lobular, 330 mucinous and 117 medullary cancers were diagnosed. The effect of both age at menarche and age at first birth was greatest for lobular tumours; relative risks per 5-year increase in age at menarche for ductal, lobular, and tubular cancers were 0.93 (0.87-0.99), 0.65 (0.56-0.76), and 0.75 (0.57-0.98), respectively (P-value for heterogeneity=0.0001); and the relative risks per 5-year increase in age at first birth were 1.10 (1.07-1.12), 1.23 (1.17-1.29), and 1.13 (1.03-1.23), respectively (P-value for heterogeneity=0.0006). Increasing parity reduced the risk of each tumour type, except medullary cancers, but the reduction in risk was greater for mucinous cancers than for any other subtype considered (P<0.05 for comparison with each other subtype in turn). The effect of menopause did not vary significantly by tumour histology. Meta-analysis of published results on the effects of age at menarche and age at first birth on ductal and lobular cancers were in keeping with our findings.

Lifestyle factors and primary glioma and meningioma tumours in the Million Women Study cohort.

Previous studies have reported inconsistent results on the effect of anthropometric and lifestyle factors on the risk of developing glioma or meningioma tumours. A prospective cohort of 1.3 million middle-aged women was used to examine these relationships. During 7.7 million women-years of follow-up, a total of 1563 women were diagnosed with a primary incident central nervous system tumour: 646 tumours were classified as glioma and 390 as meningioma. Our results show that height is related to the incidence of all central nervous system tumours with a risk of about 20% per 10 cm increase in height (relative risk=1.19, 95% CI=1.10-1.30 per 10 cm increase in height, P<0.001): the risks did not differ significantly between specified glioma and meningioma. Body mass index (BMI) was also related to central nervous system tumour incidence, with a risk of about 20% per 10 kg m(-2) increase in BMI (relative risk=1.17, 95% CI=1.03-1.34 per 10 kg m(-2) increase in BMI, P=0.02). Smoking status, alcohol intake, socioeconomic level, parity, age at first birth, and oral contraceptive use were not associated with the risk of glioma or meningioma tumours. In conclusion, for women in the United Kingdom, the incidence of glioma or meningioma tumours increases with increasing height and increasing BMI.

Active and passive smoking and the risk of breast cancer in women aged 36-45 years: a population based case-control study in the UK.

Active smoking has little or no effect on breast cancer risk but some investigators have suggested that passive smoking and its interaction with active smoking may be associated with an increased risk. In a population based case-control study of breast cancer in women aged 36-45 years at diagnosis, information on active smoking, passive smoking in the home, and other factors, was collected at interview from 639 cases and 640 controls. Women were categorised jointly by their active and passive smoking exposure. Among never smoking controls, women who also reported no passive smoking exposure were significantly more likely to be nulliparous and to be recent users of oral contraceptives. Among those never exposed to passive smoking, there was no significant association between active smoking and breast cancer, relative risk (RR) of 1.12 (95% confidence interval (CI) 0.72-1.73) for past smokers and RR of 1.19 (95% CI 0.72-1.95) for current smokers, nor was there an association with age started, duration or intensity of active smoking. Compared with women who were never active nor passive smokers, there was no significant association between passive smoking in the home and breast cancer risk in never smokers, RR of 0.89 (95% CI 0.64-1.25), in past smokers, RR of 1.09 (95% CI 0.75-1.56), or in current smokers, RR of 0.93 (95% CI 0.67-1.30). There was no trend with increasing duration of passive smoking and there was no heterogeneity among any of the subgroups examined. In this study, there was no evidence of an association between either active smoking or passive smoking in the home and risk of breast cancer.