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Hemmingsson, Oskar
Publications (10 of 16) Show all publications
Baumeister, S. E., Schlesinger, S., Aleksandrova, K., Jochem, C., Jenab, M., Gunter, M. J., . . . Leitzmann, M. F. (2019). Association between physical activity and risk of hepatobiliary cancers: A multinational cohort study. Journal of Hepatology, 70(5), 885-892
Open this publication in new window or tab >>Association between physical activity and risk of hepatobiliary cancers: A multinational cohort study
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2019 (English)In: Journal of Hepatology, ISSN 0168-8278, E-ISSN 1600-0641, Vol. 70, no 5, p. 885-892Article in journal (Refereed) Published
Abstract [en]

Background & Aims: To date, evidence on the association between physical activity and risk of hepatobiliary cancers has been inconclusive. We examined this association in the European Prospective Investigation into Cancer and Nutrition cohort (EPIC).

Methods: We identified 275 hepatocellular carcinoma (HCC) cases, 93 intrahepatic bile duct cancers (IHBCs), and 164 non-gallbladder extrahepatic bile duct cancers (NGBCs) among 467,336 EPIC participants (median follow-up 14.9 years). We estimated cause-specific hazard ratios (HRs) for total physical activity and vigorous physical activity and performed mediation analysis and secondary analyses to assess robustness to confounding (e.g. due to hepatitis virus infection).

Results: In the EPIC cohort, the multivariable-adjusted HR of HCC was 0.55 (95% CI 0.38–0.80) comparing active and inactive individuals. Regarding vigorous physical activity, for those reporting >2 hours/week compared to those with no vigorous activity, the HR for HCC was 0.50 (95% CI 0.33–0.76). Estimates were similar in sensitivity analyses for confounding. Total and vigorous physical activity were unrelated to IHBC and NGBC. In mediation analysis, waist circumference explained about 40% and body mass index 30% of the overall association of total physical activity and HCC.

Conclusions: These findings suggest an inverse association between physical activity and risk of HCC, which is potentially mediated by obesity.

Lay summary: In a pan-European study of 467,336 men and women, we found that physical activity is associated with a reduced risk of developing liver cancers over the next decade. This risk was independent of other liver cancer risk factors, and did not vary by age, gender, smoking status, body weight, and alcohol consumption.

Keywords
Hepatobiliary cancer, Hepatocellular carcinoma, Liver cancer, Physical activity
National Category
Public Health, Global Health, Social Medicine and Epidemiology
Identifiers
urn:nbn:se:umu:diva-158366 (URN)10.1016/j.jhep.2018.12.014 (DOI)000464016500012 ()30582978 (PubMedID)
Available from: 2019-04-29 Created: 2019-04-29 Last updated: 2019-04-29Bibliographically approved
Bradbury, K. E., Appleby, P. N., Tipper, S. J., Travis, R. C., Allen, N. E., Kvaskoff, M., . . . Key, T. J. (2019). Circulating insulin-like growth factor I in relation to melanoma risk in the European prospective investigation into cancer and nutrition. International Journal of Cancer, 144(5), 957-966
Open this publication in new window or tab >>Circulating insulin-like growth factor I in relation to melanoma risk in the European prospective investigation into cancer and nutrition
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2019 (English)In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 144, no 5, p. 957-966Article in journal (Refereed) Published
Abstract [en]

Insulin-like growth factor-I (IGF-I) regulates cell proliferation and apoptosis, and is thought to play a role in tumour development. Previous prospective studies have shown that higher circulating concentrations of IGF-I are associated with a higher risk of cancers at specific sites, including breast and prostate. No prospective study has examined the association between circulating IGF-I concentrations and melanoma risk. A nested case-control study of 1,221 melanoma cases and 1,221 controls was performed in the European Prospective Investigation into Cancer and Nutrition cohort, a prospective cohort of 520,000 participants recruited from 10 European countries. Conditional logistic regression was used to estimate odds ratios (ORs) for incident melanoma in relation to circulating IGF-I concentrations, measured by immunoassay. Analyses were conditioned on the matching factors and further adjusted for age at blood collection, education, height, BMI, smoking status, alcohol intake, marital status, physical activity and in women only, use of menopausal hormone therapy. There was no significant association between circulating IGF-I concentration and melanoma risk (OR for highest vs lowest fifth = 0.93 [95% confidence interval [CI]: 0.71 to 1.22]). There was no significant heterogeneity in the association between IGF-I concentrations and melanoma risk when subdivided by gender, age at blood collection, BMI, height, age at diagnosis, time between blood collection and diagnosis, or by anatomical site or histological subtype of the tumour (Pheterogeneity≥0.078). We found no evidence for an association between circulating concentrations of IGF-I measured in adulthood and the risk of melanoma.

Place, publisher, year, edition, pages
John Wiley & Sons, 2019
Keywords
EPIC, biomarker, height, insulin-like growth factor I, melanoma, prospective studies
National Category
Surgery
Identifiers
urn:nbn:se:umu:diva-154639 (URN)10.1002/ijc.31854 (DOI)000455041700004 ()30191956 (PubMedID)
Funder
Swedish Cancer SocietySwedish Research Council
Available from: 2018-12-21 Created: 2018-12-21 Last updated: 2019-02-11Bibliographically approved
Caini, S., Masala, G., Saieva, C., Kvaskoff, M., Sacerdote, C., Savoye, I., . . . Palli, D. (2017). Coffee, tea and melanoma risk: findings from the European Prospective Investigation into Cancer and Nutrition. International Journal of Cancer, 140(10), 2246-2255
Open this publication in new window or tab >>Coffee, tea and melanoma risk: findings from the European Prospective Investigation into Cancer and Nutrition
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2017 (English)In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 140, no 10, p. 2246-2255Article in journal (Refereed) Published
Abstract [en]

What's new? Laboratory studies suggest that coffee and tea protect against melanoma, but epidemiological findings are inconsistent. Here the authors studied more than 400,000 participants within the European Prospective Investigation into Cancer and Nutrition (EPIC) and confirmed an inverse association between caffeinated coffee consumption and melanoma risk. No association was found with decaffeinated coffee or tea. Interestingly, drinking coffee only protected men, but not women, from developing the often fatal skin cancer, raising interesting questions about gender-specific hormones or coffee habits influencing this association. In vitro and animal studies suggest that bioactive constituents of coffee and tea may have anticarcinogenic effects against cutaneous melanoma; however, epidemiological evidence is limited to date. We examined the relationships between coffee (total, caffeinated or decaffeinated) and tea consumption and risk of melanoma in the European Prospective Investigation into Cancer and Nutrition (EPIC). EPIC is a multicentre prospective study that enrolled over 500,000 participants aged 25-70 years from ten European countries in 1992-2000. Information on coffee and tea drinking was collected at baseline using validated country-specific dietary questionnaires. We used adjusted Cox proportional hazards regression models to calculate hazard ratios (HR) and 95% confidence intervals (95% CI) for the associations between coffee and tea consumption and melanoma risk. Overall, 2,712 melanoma cases were identified during a median follow-up of 14.9 years among 476,160 study participants. Consumption of caffeinated coffee was inversely associated with melanoma risk among men (HR for highest quartile of consumption vs. non-consumers 0.31, 95% CI 0.14-0.69) but not among women (HR 0.96, 95% CI 0.62-1.47). There were no statistically significant associations between consumption of decaffeinated coffee or tea and the risk of melanoma among both men and women. The consumption of caffeinated coffee was inversely associated with melanoma risk among men in this large cohort study. Further investigations are warranted to confirm our findings and clarify the possible role of caffeine and other coffee compounds in reducing the risk of melanoma.

National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-134695 (URN)10.1002/ijc.30659 (DOI)000399313200008 ()28218395 (PubMedID)
Available from: 2017-06-30 Created: 2017-06-30 Last updated: 2018-06-09Bibliographically approved
Fedirko, V., Tran, H. Q., Gewirtz, A. T., Stepien, M., Trichopoulou, A., Aleksandrova, K., . . . Jenab, M. (2017). Exposure to bacterial products lipopolysaccharide and flagellin and hepatocellular carcinoma: a nested case-control study. BMC Medicine, 72(15)
Open this publication in new window or tab >>Exposure to bacterial products lipopolysaccharide and flagellin and hepatocellular carcinoma: a nested case-control study
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2017 (English)In: BMC Medicine, ISSN 1741-7015, E-ISSN 1741-7015, Vol. 72, no 15Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Leakage of bacterial products across the gut barrier may play a role in liver diseases which often precede the development of liver cancer. However, human studies, particularly from prospective settings, are lacking.

METHODS: We used a case-control study design nested within a large prospective cohort to assess the association between circulating levels of anti-lipopolysaccharide (LPS) and anti-flagellin immunoglobulin A (IgA) and G (IgG) (reflecting long-term exposures to LPS and flagellin, respectively) and risk of hepatocellular carcinoma. A total of 139 men and women diagnosed with hepatocellular carcinoma between 1992 and 2010 were matched to 139 control subjects. Multivariable rate ratios (RRs), including adjustment for potential confounders, hepatitis B/C positivity, and degree of liver dysfunction, were calculated with conditional logistic regression.

RESULTS:  = 0.021). This finding did not vary substantially by time from enrollment to diagnosis, and did not change after adjustment for chronic infection with hepatitis B and C viruses.

CONCLUSIONS: These novel findings, based on exposures up to several years prior to diagnosis, support a role for gut-derived bacterial products in hepatocellular carcinoma development. Further study into the role of gut barrier failure and exposure to bacterial products in liver diseases is warranted.

Place, publisher, year, edition, pages
BioMed Central, 2017
Keywords
Endotoxins, Flagellin, Hepatocellular carcinoma, Lipopolysaccharide, Prospective studies
National Category
Clinical Medicine
Identifiers
urn:nbn:se:umu:diva-146516 (URN)10.1186/s12916-017-0830-8 (DOI)000398034900001 ()28372583 (PubMedID)
Funder
Swedish Cancer SocietyRegion SkåneVästerbotten County Council
Available from: 2018-04-11 Created: 2018-04-11 Last updated: 2018-10-16Bibliographically approved
Rutegård, M., Hassmén, N., Hemmingsson, O., Haapamäki, M. M., Matthiessen, P. & Rutegård, J. (2016). Anterior Resection for Rectal Cancer and Visceral Blood Flow: An Explorative Study. Scandinavian Journal of Surgery, 105(2), 78-83
Open this publication in new window or tab >>Anterior Resection for Rectal Cancer and Visceral Blood Flow: An Explorative Study
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2016 (English)In: Scandinavian Journal of Surgery, ISSN 1457-4969, E-ISSN 1799-7267, Vol. 105, no 2, p. 78-83Article in journal (Refereed) Published
Abstract [en]

BACKGROUND AND AIMS: Impaired blood perfusion may be implicated in anastomotic leakage after anterior resection for rectal cancer. We investigated whether high ligation of the inferior mesenteric artery or total mesorectal excision compromises visceral blood flow in the colonic limb and the rectal stump, respectively.

MATERIAL AND METHODS: A prospective cohort study was conducted in a university hospital setting. We used Laser Doppler flowmetry to evaluate the impact of level of tie on colonic limb perfusion and the extent of the mesorectal excision on the rectal blood flow. In the rectum, different quadrants were also assessed. The Mann-Whitney U test was used to compare mean blood flow ratios between groups.

RESULTS: Some 23 patients were recruited in a convenience sample during a period in 2012-2013. The mean blood flow ratio was not decreased after high tie compared to low tie surgery (1.71 vs 1.19; p = 0.28). Total mesorectal excision reduced the mean blood flow ratio in the rectum, as compared with partial mesorectal excision (0.76 vs 1.28; p = 0.14). This was especially pronounced in the posterior aspect of the rectum (0.66 vs 1.68; p = 0.02).

CONCLUSION: High tie ligation did not seem to decrease colonic limb perfusion, while total mesorectal excision may decrease rectal blood flow. The posterior quadrant of the rectum might be particularly vulnerable to the dissection involved in total mesorectal excision.

Keywords
Inferior mesenteric artery, left colic artery, mesorectal excision, high tie, Laser Doppler flowmetry
National Category
Surgery
Identifiers
urn:nbn:se:umu:diva-120694 (URN)10.1177/1457496915593692 (DOI)000375715400003 ()26250353 (PubMedID)
Available from: 2016-05-18 Created: 2016-05-18 Last updated: 2018-06-07Bibliographically approved
Duarte-Salles, T., Misra, S., Stepien, M., Plymoth, A., Muller, D., Overvad, K., . . . Beretta, L. (2016). Circulating Osteopontin and Prediction of Hepatocellular Carcinoma Development in a Large European Population. Cancer Prevention Research, 9(9), 758-765
Open this publication in new window or tab >>Circulating Osteopontin and Prediction of Hepatocellular Carcinoma Development in a Large European Population
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2016 (English)In: Cancer Prevention Research, ISSN 1940-6207, E-ISSN 1940-6215, Vol. 9, no 9, p. 758-765Article in journal (Refereed) Published
Abstract [en]

We previously identified osteopontin (OPN) as a promising marker for the early detection of hepatocellular carcinoma (HCC). In this study, we investigated the association between prediagnostic circulating OPN levels and HCC incidence in a large population-based cohort. A nested case-control study was conducted within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. During a mean follow-up of 4.8 years, 100 HCC cases were identified. Each case was matched to two controls and OPN levels were measured in baseline plasma samples. Viral hepatitis, liver function, and a-fetoprotein (AFP) tests were also conducted. Conditional logistic regression models were used to calculate multivariable odds ratio (OR) and 95% confidence intervals (95% CI) for OPN levels in relation to HCC. Receiver operating characteristics curves were constructed to determine the discriminatory accuracy of OPN alone or in combination with other liver biomarkers in the prediction of HCC. OPN levels were positively associated with HCC risk (per 10% increment, ORmultivariable = 1.30; 95% CI, 1.14-1.48). The association was stronger among cases diagnosed within 2 years of follow-up. Adding liver function tests to OPN improved the discriminatory performance for subjects who developed HCC (AUC = 0.86). For cases diagnosed within 2 years, the combination of OPN and AFP was best able to predict HCC risk (AUC = 0.88). The best predictive model for HCC in this low-risk population is OPN in combination with liver function tests. Within 2 years of diagnosis, the combination of OPN and AFP best predicted HCC development, suggesting that measuring OPN and AFP could identify high-risk groups independently of a liver disease diagnosis.

National Category
Surgery
Identifiers
urn:nbn:se:umu:diva-126502 (URN)10.1158/1940-6207.CAPR-15-0434 (DOI)000383090500006 ()27339170 (PubMedID)
Available from: 2016-10-27 Created: 2016-10-10 Last updated: 2018-06-09Bibliographically approved
Hughes, D. J., Duarte-Salles, T., Hybsier, S., Trichopoulou, A., Stepien, M., Aleksandrova, K., . . . Jenab, M. (2016). Prediagnostic selenium status and hepatobiliary cancer risk in the European Prospective Investigation into Cancer and Nutrition cohort. American Journal of Clinical Nutrition, 104(2), 406-414
Open this publication in new window or tab >>Prediagnostic selenium status and hepatobiliary cancer risk in the European Prospective Investigation into Cancer and Nutrition cohort
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2016 (English)In: American Journal of Clinical Nutrition, ISSN 0002-9165, E-ISSN 1938-3207, Vol. 104, no 2, p. 406-414Article in journal (Refereed) Published
Abstract [en]

Background: Selenium status is suboptimal in many Europeans and may be a risk factor for the development of various cancers, including those of the liver and biliary tract.

Objective: We wished to examine whether selenium status in advance of cancer onset is associated with hepatobiliary cancers in the EPIC (European Prospective Investigation into Cancer and Nutrition) study.

Design: We assessed prediagnostic selenium status by measuring serum concentrations of selenium and selenoprotein P (SePP; the major circulating selenium transfer protein) and examined the association with hepatocellular carcinoma (HCC; n = 121), gallbladder and biliary tract cancers (GBTCs; n = 100), and intrahepatic bile duct cancer (IHBC; n = 40) risk in a nested case-control design within the EPIC study. Selenium was measured by total reflection X-ray fluorescence, and SePP was determined by a colorimetric sandwich ELISA. Multivariable ORs and 95% CIs were calculated by using conditional logistic regression.

Results: HCC and GBTC cases, but not IHBC cases, showed significantly lower circulating selenium and SePP concentrations than their matched controls. Higher circulating selenium was associated with a significantly lower HCC risk (OR per 20-mg/L increase: 0.41; 95% CI: 0.23, 0.72) but not with the risk of GBTC or IHBC. Similarly, higher SePP concentrations were associated with lowered HCC risk only in both the categorical and continuous analyses (HCC: P-trend <= 0.0001; OR per 1.5-mg/L increase: 0.37; 95% CI: 0.21, 0.63).

Conclusion: These findings from a large prospective cohort provide evidence that suboptimal selenium status in Europeans may be associated with an appreciably increased risk of HCC development.

Keywords
hepatocellular carcinoma, selenium, selenoprotein P, prospective cohort, liver cancer, hepatobiliary ncer, selenium status
National Category
Cancer and Oncology Nutrition and Dietetics
Identifiers
urn:nbn:se:umu:diva-126626 (URN)10.3945/ajcn.116.131672 (DOI)000381870200021 ()27357089 (PubMedID)
Available from: 2016-11-22 Created: 2016-10-12 Last updated: 2018-06-09Bibliographically approved
Boussemart, L., Malka-Mahieu, H., Girault, I., Allard, D., Hemmingsson, O., Tomasic, G., . . . Vagner, S. (2014). eIF4F is a nexus of resistance to anti-BRAF and anti-MEK cancer therapies. Nature, 513(7516), 105-109
Open this publication in new window or tab >>eIF4F is a nexus of resistance to anti-BRAF and anti-MEK cancer therapies
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2014 (English)In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 513, no 7516, p. 105-109Article in journal (Refereed) Published
Abstract [en]

In BRAF(V600)-mutant tumours, most mechanisms of resistance to drugs that target the BRAF and/or MEK kinases rely on reactivation of the RAS-RAF-MEK-ERK mitogen-activated protein kinase (MAPK) signal transduction pathway, on activation of the alternative, PI(3)K-AKT-mTOR, pathway (which is ERK independent) or on modulation of the caspase-dependent apoptotic cascade. All three pathways converge to regulate the formation of the eIF4F eukaryotic translation initiation complex, which binds to the 7-methylguanylate cap (m(7)G) at the 5' end of messenger RNA, thereby modulating the translation of specific mRNAs. Here we show that the persistent formation of the eIF4F complex, comprising the eIF4E cap-binding protein, the eIF4G scaffolding protein and the eIF4A RNA helicase, is associated with resistance to anti-BRAF, anti-MEK and anti-BRAF plus anti-MEK drug combinations in BRAF(V600)-mutant melanoma, colon and thyroid cancer cell lines. Resistance to treatment and maintenance of eIF4F complex formation is associated with one of three mechanisms: reactivation of MAPK signalling, persistent ERK-independent phosphorylation of the inhibitory eIF4E-binding protein 4EBP1 or increased pro-apoptotic BCL-2-modifying factor (BMF)-dependent degradation of eIF4G. The development of an in situ method to detect the eIF4E-eIF4G interactions shows that eIF4F complex formation is decreased in tumours that respond to anti-BRAF therapy and increased in resistant metastases compared to tumours before treatment. Strikingly, inhibiting the eIF4F complex, either by blocking the eIF4E-eIF4G interaction or by targeting eIF4A, synergizes with inhibiting BRAF(V600) to kill the cancer cells. eIF4F not only appears to be an indicator of both innate and acquired resistance but also is a promising therapeutic target. Combinations of drugs targeting BRAF (and/or MEK) and eIF4F may overcome most of the resistance mechanisms arising in BRAF(V600)-mutant cancers.

National Category
Cell and Molecular Biology
Identifiers
urn:nbn:se:umu:diva-96743 (URN)10.1038/nature13572 (DOI)000341174800039 ()25079330 (PubMedID)
Available from: 2014-12-01 Created: 2014-12-01 Last updated: 2018-06-07Bibliographically approved
Natarajan, B., Gaur, R., Hemmingsson, O., Kao, G. & Naredi, P. (2013). Depletion of the ER chaperone ENPL-1 sensitizes C. elegans to the anticancer drug cisplatin. Worm, 2(1), Article ID e24059.
Open this publication in new window or tab >>Depletion of the ER chaperone ENPL-1 sensitizes C. elegans to the anticancer drug cisplatin
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2013 (English)In: Worm, ISSN 2162-4046, Vol. 2, no 1, article id e24059Article in journal (Refereed) Published
Abstract [en]

Cisplatin is an essential chemotherapeutic drug in the treatment of many cancers. Its use, however, is limited by the development of resistance in many tumors. The ability to re-sensitize resistant tumors could significantly strengthen cisplatin therapy in patients. Caenorhabditis elegans is a suitable model for studying the cytoplasmic role of cisplatin in tumor cells. We have previously shown that the ATPase ASNA-1 has similar roles as a factor governing cisplatin sensitivity in mammalian tumor cells and C. elegans. Here we study the endoplasmic reticulum (ER) resident chaperone ENPL-1/GRP94 and find that its depletion makes worms sensitive to cisplatin. Elevated ER stress levels in enpl-1 mutants is the likely cause of this sensitivity because a correlation can be made between cisplatin sensitivity and the high ER stress levels. We also find that asna-1 mutants have elevated unfolded protein response (UPR) activity and that the intrinsically cisplatin resistant wild-type worms become sensitive when ER stress is high. We conclude that enpl-1 is a cisplatin sensitizing factor and suggest that manipulation of its levels or of UPR activity will enhance the effects of cisplatin based cancer therapy.

Place, publisher, year, edition, pages
Landes Bioscience, 2013
Keywords
cisplatin, unfolded protein response, GRP94, asna-1, endoplasmic reticulum stress
National Category
Surgery Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-90974 (URN)10.4161/worm.24059 (DOI)24058864 (PubMedID)
Available from: 2014-07-04 Created: 2014-07-04 Last updated: 2018-06-07Bibliographically approved
Rutegård, M., Hemmingsson, O., Matthiessen, P. & Rutegård, J. (2012). High tie in anterior resection for rectal cancer confers no increased risk of anastomotic leakage. British Journal of Surgery, 99(1), 127-132
Open this publication in new window or tab >>High tie in anterior resection for rectal cancer confers no increased risk of anastomotic leakage
2012 (English)In: British Journal of Surgery, ISSN 0007-1323, E-ISSN 1365-2168, Vol. 99, no 1, p. 127-132Article in journal (Refereed) Published
Abstract [en]

Background: It is controversial whether division of the inferior mesenteric artery close to the aorta influences the risk of anastomotic leakage, especially in the elderly and unfit. This population-based study was carried out to evaluate the independent association between a high arterial ligation and anastomotic leakage in anterior resection for rectal cancer. Methods: All patients who had anterior resection for rectal cancer from 2007 to 2009 inclusive were identified in the Swedish Colorectal Cancer Registry. The association between high tie and anastomotic leakage was evaluated in a logistic regression model, with adjustment for confounders. Stratification was performed for co-morbidity as judged by the American Society of Anesthesiologists (ASA) classification. Results: Symptomatic anastomotic leakage occurred in 81 (9.9 per cent) of 818 patients with a high tie and 108 (9.8 per cent) of 1101 without. Overall, the use of a high tie was not associated with a higher risk of anastomotic leakage (odds ratio (OR) 1.00, 95 per cent confidence interval 0.72 to 1.39). There was no increased risk in patients classifed as ASA grade I or II (OR 0.97, 0.69 to 1.35), or in those graded ASA III or IV (OR 1.26, 0.58 to 2.75). Conclusion: In the present population-based setting, use of a high tie was not associated with an increased rate of symptomatic anastomotic leakage.

Place, publisher, year, edition, pages
Malden, MA: Wiley-Blackwell, 2012
National Category
Surgery
Identifiers
urn:nbn:se:umu:diva-55541 (URN)10.1002/bjs.7712 (DOI)000303147800021 ()
Available from: 2012-05-25 Created: 2012-05-21 Last updated: 2018-06-08Bibliographically approved
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