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  • 1. Andersson, Y.
    et al.
    Frisell, J.
    Sylvan, M.
    de Boniface, J.
    Bergkvist, Leif
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Causes of false-negative sentinel node biopsy in patients with breast cancer2013In: British Journal of Surgery, ISSN 0007-1323, E-ISSN 1365-2168, Vol. 100, no 6, p. 775-783Article in journal (Refereed)
    Abstract [en]

    Background: Sentinel lymph node (SLN) biopsy has replaced axillary lymph node dissection as the routine staging procedure in clinically node-negative breast cancer. False-negative SLN biopsy results in misclassification and may cause undertreatment of the disease. The aim of this study was to investigate whether serial sectioning of SLNs reveals metastases more frequently in patients with false-negative SLNs than in patients with true-negative SLNs. Methods: This was a case-control study. Tissue blocks from patients with false-negative SLNs, defined as tumour-positive lymph nodes excised at completion axillary dissection or a subsequent axillary tumour recurrence, were reassessed by serial sectioning and immunohistochemical staining. For each false-negative node, two true-negative SLN biopsies were analysed. Tumour and node characteristics in patients with false-negative SLNs were compared with those in patients with a positive SLN by univariable and multivariable regression analysis. Results: Undiagnosed SLN metastases were discovered in nine (18 per cent) of 50 patients in the false-negative group and in 12 (11.2 per cent) of 107 patients in the true-negative group (P = 0.245). The metastases were represented by isolated tumour cells in 14 of these 21 patients. The risk of a false-negative SLN was higher in patients with hormone receptor-negative (odds ratio (OR) 2.50, 95 per cent confidence interval 1.17 to 5.33) or multifocal tumours (OR 3.39, 1.71 to 6.71), or if only one SLN was identified (OR 3.57, 1.98 to 6.45). Conclusion: SLN serial sectioning contributes to a higher rate of detection of SLN metastasis. The rate of upstaging of the tumour is similar in false-and true-negative groups of patients.

  • 2.
    Andersson, Yvette
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland. Vastmanland Cty Hosp, Dept Surg, S-72189 Vasteras, Sweden.
    Bergkvist, Leif
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland. Vastmanland Cty Hosp, Dept Surg, S-72189 Vasteras, Sweden.
    Frisell, J.
    Karolinska Univ Hosp, Dept Breast & Endocrine Surg, Stockholm, Sweden;Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden.
    de Boniface, J.
    Capio St Gorans Hosp, Dept Surg, Stockholm, Sweden;Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden.
    Long-term breast cancer survival in relation to the metastatic tumor burden in axillary lymph nodes2018In: Breast Cancer Research and Treatment, ISSN 0167-6806, E-ISSN 1573-7217, Vol. 171, no 2, p. 359-369Article in journal (Refereed)
    Abstract [en]

    Purpose: The clinical significance of lymph node micrometastases and isolated tumor cells (ITCs) in breast cancer is still controversial. After a median follow-up of 52 months, a report from the Swedish Multicenter Cohort Study presented a worse cancer-specific and event-free survival for patients with micrometastases than node-negative individuals, but could not demonstrate a significant difference in overall survival (OS). Due to the tendency of breast cancer to relapse after more than 5-10 years, we now report the long-term survival of the cohort.

    Methods: Between September 2000 and January 2004, 3355 breast cancer patients were included in a prospective cohort. Sentinel lymph node biopsy was always performed. Patients were classified in four groups according to their overall nodal stage: node negative (N0, 2372), ITCs (113), micrometastases (123), and macrometastases (747). Kaplan-Meier survival estimates and Cox proportional hazard regression models were applied.

    Results: Median follow-up was 156 months. Ten-year cancer-specific survival and OS were significantly lower in case of micrometastases than in N0 (84.7 vs. 93.5%, p = 0.001, and 75.5 vs. 84.2%, p = 0.046, respectively). In case of macrometastases, corresponding survival rates were 82.8 and 74.3%. Only for those aged less than 50 years, cancer-specific survival and OS were significantly worse in case of ITCs than N0. Patients with micrometastases received less often chemotherapy than those with macrometastases (24.4 vs. 53.9%).

    Conclusions: Lymph node micrometastases in breast cancer have a prognostic significance. This study demonstrates a similar survival for patients with micrometastases and those with macrometastases, possibly due to systemic undertreatment.

  • 3. Andersson, Yvette
    et al.
    de Boniface, J
    Jönsson, P-E
    Ingvar, C
    Liljegren, G
    Bergkvist, Leif
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , Centre for Clinical Research, County of Västmanland.
    Frisell, J
    Axillary recurrence rate 5 years after negative sentinel node biopsy for breast cancer2012In: British Journal of Surgery, ISSN 0007-1323, E-ISSN 1365-2168, Vol. 99, no 2, p. 226-231Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Sentinel lymph node (SLN) biopsy has replaced axillary lymph node dissection (ALND) as the standard axillary staging procedure in breast cancer. Follow-up studies in SLN-negative women treated without ALND report low rates of axillary recurrence, but most studies have short follow-up, and few are multicentre studies.

    METHODS: Between September 2000 and January 2004, patients who were SLN-negative and did not have ALND were included in a prospective cohort. Kaplan-Meier estimates were used to analyse the rates of axillary recurrence and survival. The risk of axillary recurrence was also compared in centres with high and low experience with the SLN biopsy (SLNB) technique.

    RESULTS: A total of 2195 patients with 2216 breast tumours were followed for a median of 65 months. Isolated axillary recurrence was diagnosed in 1·0 per cent of patients. The event-free 5-year survival rate was 88·8 per cent and the overall 5-year survival rate 93·1 per cent. There was no difference in recurrence rates between centres contributing fewer than 150 SLNB procedures to the cohort and centres contributing 150 or more procedures.

    CONCLUSION: This study confirmed the low risk of axillary recurrence 5 years after SLNB for breast cancer without ALND.

  • 4. Andersson, Yvette
    et al.
    Frisell, J
    de Boniface, J
    Bergkvist, Leif
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Prediction of non-sentinel lymph node status in breast cancer patients with sentinel lymph node metastases: evaluation of the tenon score2012In: Breast Cancer : Basic and Clinical Research, ISSN 1178-2234, E-ISSN 1178-2234, Vol. 6, p. 31-38Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION:

    Current guidelines recommend completion axillary lymph node dissection (cALND) in case of a sentinel lymph node (SLN) metastasis larger than 0.2 mm. However, in 50%-65% of these patients, the non-SLNs contain no further metastases and cALND provides no benefit. Several nomograms and scoring systems have been suggested to predict the risk of metastases in non-SLNs. We have evaluated the Tenon score.

    PATIENTS AND METHODS:

    In a retrospective review of the Swedish Sentinel Node Multicentre Cohort Study, risk factors for additional metastases were analysed in 869 SLN-positive patients who underwent cALND, using uni- and multivariate logistic regression models. A receiver operating characteristic (ROC) curve was drawn on the basis of the sensitivity and specificity of the Tenon score, and the area under the curve (AUC) was calculated.

    RESULTS:

    Non-SLN metastases were identified in 270/869 (31.1%) patients. Tumour size and grade, SLN status and ratio between number of positive SLNs and total number of SLNs were significantly associated with non-SLN status in multivariate analyses. The area under the curve for the Tenon score was 0.65 (95% CI 0.61-0.69). In 102 patients with a primary tumour <2 cm, Elston grade 1-2 and SLN metastases ≤2 mm, the risk of non SLN metastasis was less than 10%.

    CONCLUSION:

    The Tenon score performed inadequately in our material and we could, based on tumour and SLN characteristics, only define a very small group of patients in which negative non-sentinel nodes could be predicted.

  • 5.
    Bergkvist, L
    Uppsala University, Interfaculty Units, Centre for Clinical Research.
    The rationale of surgical treatment of invasive breast cancer and decision making of surgical procedures.2002In: Scand J Surg, ISSN 1457-4969, Vol. 91, no 3, p. 240-5Article in journal (Refereed)
  • 6.
    Bergkvist, L
    et al.
    Uppsala University, Interfaculty Units, Centre for Clinical Research.
    Frisell, J
    Multicentre validation study of sentinel node biopsy for staging in breast cancer.2005In: Br J Surg, ISSN 0007-1323, Vol. 92, no 10, p. 1221-4Article in journal (Refereed)
  • 7.
    Bergkvist, Leif
    Uppsala University, Interfaculty Units, Centre for Clinical Research.
    Breast cancer and breastfeeding: collaborative reanalysis of individual data from 47 epidemiological studies in 30 countries, including 50302 women with breast cancer and 96973 women without the disease.2002In: Lancet, ISSN 0140-6736, Vol. 360, no 9328, p. 187-95Article in journal (Refereed)
  • 8.
    Bergkvist, Leif
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , Centre for Clinical Research, County of Västmanland.
    Surgical site infection among women discharged vith a drain in situ after breast cancer surgery.2007In: World Journal of Surgery, ISSN 0364-2313, E-ISSN 1432-2323, Vol. 31, no 12, p. 2300-2301Article in journal (Refereed)
  • 9.
    Bergkvist, Leif
    et al.
    Uppsala University, Interfaculty Units, Centre for Clinical Research.
    Liljegren, Göran
    Ahlgren, Johan
    Centrum för klinisk forskning, Gävleborg.
    Lidin, Annika
    Holmqvist, Marit
    Holmberg, Lars
    Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    [Registries contribute to better breast cancer care]2004In: Lakartidningen, ISSN 0023-7205, Vol. 101, no 34, p. 2579-81Article in journal (Refereed)
  • 10.
    Carlander, Johan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland. Linkoping Univ, Dept Clin & Expt Med, Linkoping, Sweden..
    Wagner, Philippe
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland. Uppsala Univ, Vastmanland Cty Hosp, Dept Surg, S-72189 Vasteras, Sweden..
    Gimm, Oliver
    Linkoping Univ, Dept Clin & Expt Med, Linkoping, Sweden.;Linkoping Univ Hosp, Dept Surg, S-58185 Linkoping, Sweden..
    Nordenstrom, Erik
    Univ Lund Hosp, Dept Surg, Malmo, Sweden..
    Jansson, Svante
    Sahlgrens Univ Hosp, Dept Surg, Gothenburg, Sweden..
    Bergkvist, Leif
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland. Uppsala Univ, Vastmanland Cty Hosp, Dept Surg, S-72189 Vasteras, Sweden..
    Johansson, Kenth
    Linkoping Univ, Dept Clin & Expt Med, Linkoping, Sweden.;Sahlgrens Univ Hosp, Dept Surg, Gothenburg, Sweden.;Vastervik Hosp, Dept Surg, Vastervik, Sweden..
    Risk of Complications with Energy-Based Surgical Devices in Thyroid Surgery: A National Multicenter Register Study2016In: World Journal of Surgery, ISSN 0364-2313, E-ISSN 1432-2323, Vol. 40, no 1, p. 117-123Article in journal (Refereed)
    Abstract [en]

    Energy-based surgical devices (EBD) combining cutting and coagulation are increasingly used in thyroid surgery. However, there is a lack of information about potential benefits and risk of complications outside controlled trials. The aims of this national multicenter register study were to describe the use of EDB, their potential effect on complication rates, and on operation time. The Scandinavian Quality Register for Thyroid and Parathyroid surgery includes 35 surgical units in Sweden and covered 88 % of the thyroid procedures performed during 2008-2009. The use of the EBD was specifically registered for 12 months, and 1297 patients were included. Surgically related complications and operation time were evaluated. The clamp-and-tie group (C-A-T) constituted the control group for comparison with procedures where EBD was used. The thyroid procedures performed included C-A-T (16.6 %), bipolar electrosurgery (ES: 56.5 %), electronic vessel sealing (EVS: 12.2 %), and ultrasonic dissection (UD: 14.5 %). Mean operative time was longer with EVS (p < 0.001) and shorter with UD (p < 0.05) than in the other groups. The bipolar ES group and the EVS group had higher incidence of calcium treatment at discharge and after 6 weeks than the UD group. No significant difference in nerve injury was found between the groups. There was a significant more frequent use of topical hemostatic agents in the EBD group compared to C-A-T. In this national multicenter study, the use of UD shortened and EVS increased operating time. There was a higher risk of calcium treatment at discharge and after 6 weeks after use of EVS and bipolar ES than after UD use. There was a significant more frequent use of topical hemostatic agents in the EBD groups compared to C-A-T.

  • 11. Celebioglu, F
    et al.
    Sylvan, M
    Perbeck, L
    Bergkvist, L
    Uppsala University, Interfaculty Units, Centre for Clinical Research.
    Frisell, J
    Intraoperative sentinel lymph node examination by frozen section, immunohistochemistry and imprint cytology during breast surgery - A prospective study.2006In: Eur J Cancer, ISSN 0959-8049, Vol. 42, no 5, p. 617-20Article in journal (Refereed)
  • 12. Dahl, K
    et al.
    Westlin, J
    Kraaz, W
    Winqvist, O
    Bergkvist, L
    Uppsala University, Interfaculty Units, Centre for Clinical Research.
    Thörn, M
    Identification of sentinel nodes in patients with colon cancer.2005In: Eur J Surg Oncol, ISSN 0748-7983, Vol. 31, no 4, p. 381-5Article in journal (Refereed)
  • 13.
    Dalberg, K
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Johansson, H
    Signomklao, T
    Rutqvist, L E
    Bergkvist, Leif
    Interfaculty Units, Centre for Clinical Research.
    Frisell, J
    Liljegren, G
    Ambre, T
    Sandelin, K
    A randomised study of axillary drainage and pectoral fascia preservation after mastectomy for breast cancer.2004In: Eur J Surg Oncol, ISSN 0748-7983, Vol. 30, no 6, p. 602-9Article in journal (Refereed)
  • 14.
    de Boniface, J.
    et al.
    Karolinska Inst, Dept Mol Med & Surg, SE-17176 Stockholm, Sweden.;Karolinska Univ Hosp, Dept Breast & Endocrine Surg, Stockholm, Sweden..
    Frisell, J.
    Karolinska Inst, Dept Mol Med & Surg, SE-17176 Stockholm, Sweden.;Karolinska Univ Hosp, Dept Breast & Endocrine Surg, Stockholm, Sweden..
    Bergkvist, Leif
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland. Vastmanland Cty Hosp, Dept Surg, Vasteras, Sweden..
    Andersson, Yvette
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland. Vastmanland Cty Hosp, Dept Surg, Vasteras, Sweden..
    Ten-year report on axillary recurrence after negative sentinel node biopsy for breast cancer from the Swedish Multicentre Cohort Study2017In: British Journal of Surgery, ISSN 0007-1323, E-ISSN 1365-2168, Vol. 104, no 3, p. 238-247Article in journal (Refereed)
    Abstract [en]

    Background: The omission of axillary lymph node dissection (ALND) in patients with breast cancer with a negative finding on sentinel node biopsy (SNB) has reduced armmorbidity substantially. Early follow-up reports have shown the rate of axillary recurrence to be significantly lower than expected, with a median false-negative rate of 7 per cent for SNB. Long-term follow-up is needed as recurrences may develop late.

    Methods: The Swedish Multicentre Cohort Study included 3518 women with breast cancer and a clinically negative axilla, in whom SNB was planned. ALND was performed only in patients with sentinel node metastasis. Twenty-six centres contributed to enrolment between September 2000 and January 2004. The primary endpoint was the axillary recurrence rate and the secondary endpoint was breast cancer-specific survival, calculated using Kaplan-Meier survival estimates.

    Results: Some 2216 sentinel node-negative patients with 2237 breast cancers were analysed. The median follow-up time was 126 (range 0-174) months. Isolated axillary recurrence was found in 35 patients (1.6 per cent). High histological grade and multifocal tumours were risk factors for axillary recurrence, whereas the removal of more than two sentinel nodes decreased the risk. Fourteen (40 per cent) of 35 patients died as a consequence of axillary recurrence.

    Conclusion: The risk of axillary recurrence remains lower than expected after a negative finding on SNB at 10-year follow-up. Axillary recurrences may occur long after primary surgery, and lead to a significant risk of breast cancer death.

  • 15.
    de Boniface, Jana
    et al.
    Capio St Gorans Hosp, Dept Surg, Stockholm, Sweden.;Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden..
    Frisell, Jan
    Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden.;Karolinska Univ Hosp, Dept Breast & Endocrine Surg, Stockholm, Sweden..
    Andersson, Yvette
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland. Vastmanland Cty Hosp, Dept Surg, Vasteras, Sweden.
    Bergkvist, Leif
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Ahlgren, Johan
    Univ Orebro, Dept Oncol, Orebro, Sweden..
    Ryden, Lisa
    Lund Univ, Inst Clin Sci, Dept Surg, Lund, Sweden.;Skane Univ Hosp, Dept Surg, Lund, Sweden..
    Bagge, Roger Olofsson
    Univ Gothenburg, Sahlgrenska Univ Hosp, Inst Clin Sci, Dept Surg,Sahlgrenska Acad, Gothenburg, Sweden..
    Sund, Malin
    Norrland Univ Hosp, Surg Ctr, Umea, Sweden.;Umea Univ, Dept Surg & Perioperat Sci, Umea, Sweden..
    Johansson, Hemming
    Karolinska Inst, Clin Trials Off, Dept Oncol Pathol, Stockholm, Sweden..
    Lundstedt, Dan
    Sahlgrens Univ Hosp, Dept Oncol, Gothenburg, Sweden..
    Survival and axillary recurrence following sentinel node-positive breast cancer without completion axillary lymph node dissection: the randomized controlled SENOMAC trial2017In: BMC Cancer, ISSN 1471-2407, E-ISSN 1471-2407, Vol. 17, article id 379Article in journal (Refereed)
    Abstract [en]

    Background: The role of axillary lymph node dissection (ALND) has increasingly been called into question among patients with positive sentinel lymph nodes. Two recent trials have failed to show a survival difference in sentinel node-positive breast cancer patients who were randomized either to undergo completion ALND or not. Neither of the trials, however, included breast cancer patients undergoing mastectomy or those with tumors larger than 5 cm, and power was debatable to show a small survival difference.

    Methods: The prospective randomized SENOMAC trial includes clinically node-negative breast cancer patients with up to two macrometastases in their sentinel lymph node biopsy. Patients with T1-T3 tumors are eligible as well as patients prior to systemic neoadjuvant therapy. Both breast-conserving surgery and mastectomy, with or without breast reconstruction, are eligible interventions. Patients are randomized 1: 1 to either undergo completion ALND or not by a web-based randomization tool. This trial is designed as a non-inferiority study with breast cancer-specific survival at 5 years as the primary endpoint. Target accrual is 3500 patients to achieve 80% power in being able to detect a potential 2.5% deterioration of the breast cancer-specific 5-year survival rate. Follow-up is by annual clinical examination and mammography during 5 years, and additional controls after 10 and 15 years. Secondary endpoints such as arm morbidity and health-related quality of life are measured by questionnaires at 1, 3 and 5 years.

    Discussion: Several large subgroups of breast cancer patients, such as patients undergoing mastectomy or those with larger tumors, have not been included in key trials; however, the use of ALND is being questioned even in these groups without the support of high-quality evidence. Therefore, the SENOMAC Trial will investigate the need of completion ALND in case of limited spread to the sentinel lymph nodes not only in patients undergoing any breast surgery, but also in neoadjuvantly treated patients and patients with larger tumors.

  • 16.
    Eaker, Sonja
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Dickman, Paul W.
    Bergkvist, Leif
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , Centre for Clinical Research, County of Västmanland.
    Holmberg, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Differences in management of older women influence breast cancer survival: results from a population-based database in Sweden2006In: PLoS Medicine, ISSN 1549-1676, Vol. 3, no 3, p. e25-Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Several reports have shown that less aggressive patterns of diagnostic activity and care are provided to elderly breast carcinoma patients. We sought to investigate whether differences in the management of older women with breast cancer are associated with survival. METHODS AND FINDINGS: In an observational study using a population-based clinical breast cancer register of one health-care region in Sweden, we identified 9,059 women aged 50-84 y diagnosed with primary breast cancer between 1992 and 2002. The 5-y relative survival ratio was estimated for patients classified by age group, diagnostic activity, tumor characteristics, and treatment. The 5-y relative survival for breast cancer patients was lower (up to 13%) in women 70-84 y of age compared to women aged 50-69 y, and the difference was most pronounced in stage IIB-III and in the unstaged. Significant differences in disease management were found, as older women had larger tumors, had fewer nodes examined, and did not receive treatment by radiotherapy or by chemotherapy as often as the younger women. Adjustment for diagnostic activity, tumor characteristics, and treatment diminished the relative excess mortality in stages III and in the unstaged, whereas the excess mortality was only marginally affected in stage IIB. CONCLUSIONS: Less diagnostic activity, less aggressive treatment, and later diagnosis in older women are associated with poorer survival. The large differences in treatment of older women are difficult to explain by co-morbidity alone.

  • 17.
    Enlund, Mats
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland. Department of Anaesthesia and Intensive Care, Central Hospital, Västerås , Sweden.
    Berglund, Anders
    Andreasson, Kalle
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Cicek, Catharina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Enlund, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Bergkvist, Leif
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    The choice of anaesthetic - sevoflurane or propofol - and outcome from cancer surgery: a retrospective analysis2014In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 119, no 3, p. 251-261Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    Commonly used inhalational hypnotics, such as sevoflurane, are pro-inflammatory, whereas the intravenously administered hypnotic agent propofol is anti-inflammatory and anti-oxidative. A few clinical studies have indicated similar effects in patients. We examined the possible association between patient survival after radical cancer surgery and the use of sevoflurane or propofol anaesthesia.

    PATIENTS AND METHODS:

    Demographic, anaesthetic, and surgical data from 2,838 patients registered for surgery for breast, colon, or rectal cancers were included in a database. This was record-linked to regional clinical quality registers. Cumulative 1- and 5-year overall survival rates were assessed using the Kaplan-Meier method, and estimates were compared between patients given propofol (n = 903) or sevoflurane (n = 1,935). In a second step, Cox proportional hazard models were calculated to assess the risk of death adjusted for potential effect modifiers and confounders.

    RESULTS:

    Differences in overall 1- and 5-year survival rates for all three sites combined were 4.7% (p = 0.004) and 5.6% (p < 0.001), respectively, in favour of propofol. The 1-year survival for patients operated for colon cancer was almost 10% higher after propofol anaesthesia. However, after adjustment for several confounders, the observed differences were not statistically significant.

    CONCLUSION:

    Propofol anaesthesia might be better in surgery for some cancer types, but the retrospective design of this study, with uneven distributions of several confounders, distorted the picture. These uncertainties emphasize the need for a randomized controlled trial.

  • 18. Genkinger, Jeanine M.
    et al.
    Li, Ruifeng
    Spiegelman, Donna
    Anderson, Kristin E.
    Albanes, Demetrius
    Bergkvist, Leif
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , Centre for Clinical Research, County of Västmanland.
    Bernstein, Leslie
    Black, Amanda
    van den Brandt, Piet A.
    English, Dallas R.
    Freudenheim, Jo L.
    Fuchs, Charles S.
    Giles, Graham G.
    Giovannucci, Edward
    Goldbohm, R. Alexandra
    Horn-Ross, Pamela L.
    Jacobs, Eric J.
    Koushik, Anita
    Mannisto, Satu
    Marshall, James R.
    Miller, Anthony B.
    Patel, Alpa V.
    Robien, Kim
    Rohan, Thomas E.
    Schairer, Catherine
    Stolzenberg-Solomon, Rachael
    Wolk, Alicja
    Ziegler, Regina G.
    Smith-Warner, Stephanie A.
    Coffee, Tea, and Sugar-Sweetened Carbonated Soft Drink Intake and Pancreatic Cancer Risk: A Pooled Analysis of 14 Cohort Studies2012In: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 21, no 2, p. 305-318Article in journal (Refereed)
    Abstract [en]

    Background: Coffee has been hypothesized to have pro- and anticarcinogenic properties, whereas tea may contain anticarcinogenic compounds. Studies assessing coffee intake and pancreatic cancer risk have yielded mixed results, whereas findings for tea intake have mostly been null. Sugar-sweetened carbonated soft drink (SSB) intake has been associated with higher circulating levels of insulin, which may promote carcinogenesis. Few prospective studies have examined SSB intake and pancreatic cancer risk; results have been heterogeneous. Methods: In this pooled analysis from 14 prospective cohort studies, 2,185 incident pancreatic cancer cases were identified among 853,894 individuals during follow-up. Multivariate (MV) study-specific relative risks (RR) and 95% confidence intervals (CI) were calculated using Cox proportional hazards models and then pooled using a random-effects model. Results: No statistically significant associations were observed between pancreatic cancer risk and intake of coffee (MVRR = 1.10; 95% CI, 0.81-1.48 comparing >= 900 to <0 g/d; 237g approximate to 8oz), tea (MVRR = 0.96; 95% CI, 0.78-1.16 comparing >= 400 to 0 g/d; 237g approximate to 8oz), or SSB (MVRR = 1.19; 95% CI, 0.98-1.46 comparing >= 250 to 0 g/d; 355g approximate to 12oz; P value, test for between-studies heterogeneity > 0.05). These associations were consistent across levels of sex, smoking status, and body mass index. When modeled as a continuous variable, a positive association was evident for SSB (MVRR = 1.06; 95% CI, 1.02-1.12). Conclusion and Impact: Overall, no associations were observed for intakes of coffee or tea during adulthood and pancreatic cancer risk. Although we were only able to examine modest intake of SSB, there was a suggestive, modest positive association for risk of pancreatic cancer for intakes of SSB.

  • 19.
    Granstam Björneklett, Helena
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Lindemalm, Christina
    Immune and Gene Therapy Laboratory,Cancer Centre,Karolinska,Karolinska University Hospital.
    Ojutkangas, Marja-Leena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Berglund, Anders
    Department of Medical Epidemiology and Biostatiststics.
    Letocha, Henry
    Onkologi kliniken Västerås.
    Strang, Peter
    Karolinska Institute,SSH Stockholm.
    Bergkvist, Leif
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    A randomized controlled trial of a support group intervention on the quality of life and fatigue in women after primary treatment for early breast cancer2012In: Supportive Care in Cancer, ISSN 0941-4355, E-ISSN 1433-7339, Vol. 20, no 12, p. 3325-3334Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    When diagnosed with breast cancer, most women's lives change as well as their perspectives on and appreciation of life. The aim of the present study was to evaluate whether psychosocial support intervention could influence health-related quality of life (HRQOL) and fatigue during the first year after diagnosis.

    MATERIAL AND METHODS:

    Of 382 patients with newly diagnosed breast cancer, 191 patients were randomized to an intervention group and 191 patients were randomized to a routine control group. The intervention group received support intervention that lasted 1 week on a residential basis, followed by 4 days of follow-up 2 months later. The support intervention included informative educational parts, relaxation training, mental visualization, and nonverbal communication. HRQOL was measured using the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 and QLQ-BR23 questionnaires and fatigue with the Norwegian version of the fatigue scale at baseline and at 2, 6, and 12 months after intervention.

    RESULT:

    There was a time-dependent improvement in both functional and symptom scales between baseline and 12 months as measured by the EORTC QLQ-C30 and BR23 questionnaires and there was a decrease in fatigue between baseline and after 2 months with further improvement up to 12 months in both groups, but there were no differences between the intervention and control groups at any point in time.

    CONCLUSION:

    HRQOL improves and symptoms of fatigue decrease over time, but we could not see any additional effect from the rehabilitation program in this setting.

  • 20.
    Granstam Björneklett, Helena
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Lindemalm, Christina
    Rosenblad, Andreas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Ojutkangas, Marja-Leena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Letocha, Henry
    Strang, Peter
    Bergkvist, Leif
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    A randomised controlled trial of support group intervention after breast cancer treatment: Results on anxiety and depression2012In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 51, no 2, p. 198-207Article in journal (Refereed)
    Abstract [en]

    Background

    Previous studies have demonstrated that between 20 and 30% of women treated for breast cancer have measurable signs of anxiety and depression compared with 6% in a population of healthy women. Depression has been proposed as a predictive factor for recurrence and survival. The aim of the present study was to evaluate if psychosocial support intervention could influence anxiety and depression during the first year after diagnosis.

    Material and methods

    Newly diagnosed breast cancer patients were randomised between April 2002 and November 2007 and stratified by adjuvant chemotherapy. Of 382 eligible patients, 191 + 191 patients were randomised to intervention group or control group, respectively. Control patients were subjected to standard follow-up routines. The Intervention group had support intervention at the Foundation Lustgarden Malardalen. The rehabilitation lasted one week on a residential basis followed by four days of follow-up two months later. We used the Swedish version of the HAD scale with a cut-off value greater than 10 for clinical symptoms of depression and anxiety.

    Results

    Support group intervention lowered anxiety over time (p < 0.001) but depression was unaffected (p = 0.610).

    Conclusion

    This prospective randomised trial of support group intervention in a large homogenous group of breast cancer women showed a statistically significant effect on lowering anxiety over time. No statistically significant effect of intervention could be seen on depression.

  • 21.
    Granstam Björneklett, Helena
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Rosenblad, Andreas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Lindemalm, Christina
    Immune and Gene Therapy Laboratory,Cancer Centre,Karolinska,Karolinska University Hospital.
    Ojutkangas, Marja-Leena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Letocha, Henry
    Department of Oncology,Västmanlan County Hospital,Västerås.
    Strang, Peter
    Karolinska Institute,SSH Stockholm.
    Bergkvist, Leif
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    A randomized controlled trial of support group intervention after breast cancer treatment: Results on sick leave, health care utilization and health economy2013In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 52, no 1, p. 38-47Article in journal (Refereed)
    Abstract [en]

    Background

    More than 50% of breast cancer patients are diagnosed before the age of 65.  Returning to work after treatment is, therefore, of interest for both the individual and society. The aim was to study the effect of support group intervention on sick leave and health care utilization in economic terms.

    Material and Methods

    Of 382 patients with newly diagnosed breast cancer, 191 + 191 patients were randomized to an intervention group or to a routine control group respectively. The intervention group received support intervention on a residential basis for one week, followed by four days of follow-up two months later. The support intervention included informative-educational sections, relaxation training, mental visualization and non-verbal communication. Patients answered a questionnaire at baseline, 2, 6 and 12 months about sick leave and health care utilization.

    Result

    There was a trend towards longer sick leave and more health care utilization in the intervention group. The difference in total costs was statistically significantly higher in the intervention group after 12 months (p= 0.0036).

    Conclusion

    Costs to society were not reduced with intervention in its present form.

  • 22.
    Granstam Björneklett, Helena
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Rosenblad, Andreas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Lindemalm, Christina
    Immune and Gene Therapy Laboratory,Cancer Centre,Karolinska,Karolinska University Hospital.
    Ojutkangas, Marja-Leena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Letocha, Henry
    Onkologi kliniken Västerås.
    Strang, Peter
    Karolinska Institute,SSH Stockholm.
    Bergkvist, Leif
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Long-term follow-up of a randomized study of support group intervention in women with primary breast cancer2013In: Journal of Psychosomatic Research, ISSN 0022-3999, E-ISSN 1879-1360, Vol. 74, no 4, p. 346-353Article in journal (Refereed)
    Abstract [en]

    Background:

    Despite a fairly good prognosis, many breast-cancer patients suffer from symptoms such as anxiety, depression and fatigue, which may affect health-related quality of life and may persist for several years. The aim of the present study was to perform a long-term follow-up of a randomized study of support group intervention in women after primary breast cancer treatment.

    Materials and methods:

    Three hundred and eighty two women with primary breast cancer were randomized to support group intervention or control group, 181 in each group. Women in the intervention group participated in 1 week of intervention followed by 4 days of follow-up 2 months later. This is a long-term follow-up undertaken, in average, 6.5. years after randomization. Patients answered the questionnaires the European Organisation for Research and Treatment of Cancer, Quality of Life Questionnaire (EORTC QLQ-C30) and the Breast Cancer Module questionnaire (BR23), the Hospital Anxiety and Depression Scale (HAD) and the Norwegian version of the fatigue scale (FQ).

    Results:

    After adjusting for treatment with chemotherapy, age, marriage, education and children at home, there was a significant improvement in physical, mental and total fatigue (FQ), cognitive function, body image and future perspective (EORTC QLQ C30 and BR23) in the intervention group compared with controls. The proportion of women affected by high anxiety and depression scores were not significantly different between the groups.

    Conclusion:

    Support intervention significantly improved cognitive function, body image, future perspective and fatigue, compared with to the findings in the control group.

  • 23. Hamajima, N
    et al.
    Hirose, K
    Tajima, K
    Rohan, T
    Calle, EE
    Heath CW, Jr
    Coates, RJ
    Liff, JM
    Talamini, R
    Chantarakul, N
    Koetsawang, S
    Rachawat, D
    Morabia, A
    Schuman, L
    Stewart, W
    Szklo, M
    Bain, C
    Schofield, F
    Siskind, V
    Band, P
    Coldman, AJ
    Gallagher, RP
    Hislop, TG
    Yang, P
    Kolonel, LM
    Nomura, AM
    Hu, J
    Johnson, KC
    Mao, Y
    De Sanjose, S
    Lee, N
    Marchbanks, P
    Ory, HW
    Peterson, HB
    Wilson, HG
    Wingo, PA
    Ebeling, K
    Kunde, D
    Nishan, P
    Hopper, JL
    Colditz, G
    Gajalanski, V
    Martin, N
    Pardthaisong, T
    Silpisornkosol, S
    Theetranont, C
    Boosiri, B
    Chutivongse, S
    Jimakorn, P
    Virutamasen, P
    Wongsrichanalai, C
    Ewertz, M
    Adami, HO
    Bergkvist, L
    Magnusson, C
    Persson, I
    Chang-Claude, J
    Paul, C
    Skegg, DC
    Spears, GF
    Boyle, P
    Evstifeeva, T
    Daling, JR
    Hutchinson, WB
    Malone, K
    Noonan, EA
    Stanford, JL
    Thomas, DB
    Weiss, NS
    White, E
    Andrieu, N
    Bremond, A
    Clavel, F
    Gairard, B
    Lansac, J
    Piana, L
    Renaud, R
    Izquierdo, A
    Viladiu, P
    Cuevas, HR
    Ontiveros, P
    Palet, A
    Salazar, SB
    Aristizabel, N
    Cuadros, A
    Tryggvadottir, L
    Tulinius, H
    Bachelot, A
    Le, MG
    Peto, J
    Franceschi, S
    Lubin, F
    Modan, B
    Ron, E
    Wax, Y
    Friedman, GD
    Hiatt, RA
    Levi, F
    Bishop, T
    Kosmelj, K
    Primic-Zakelj, M
    Ravnihar, B
    Stare, J
    Beeson, WL
    Fraser, G
    Bullbrook, RD
    Cuzick, J
    Duffy, SW
    Fentiman, IS
    Hayward, JL
    Wang, DY
    McMichael, AJ
    McPherson, K
    Hanson, RL
    Leske, MC
    Mahoney, MC
    Nasca, PC
    Varma, AO
    Weinstein, AL
    Moller, TR
    Olsson, H
    Ranstam, J
    Goldbohm, RA
    van den Brandt, PA
    Apelo, RA
    Baens, J
    de la Cruz, JR
    Javier, B
    Lacaya, LB
    Ngelangel, CA
    La Vecchia, C
    Negri, E
    Marubini, E
    Ferraroni, M
    Gerber, M
    Richardson, S
    Segala, C
    Gatei, D
    Kenya, P
    Kungu, A
    Mati, JG
    Brinton, LA
    Hoover, R
    Schairer, C
    Spirtas, R
    Lee, HP
    Rookus, MA
    van Leeuwen, FE
    Schoenberg, JA
    McCredie, M
    Gammon, MD
    Clarke, EA
    Jones, L
    Neil, A
    Vessey, M
    Yeates, D
    Appleby, P
    Banks, E
    Beral, V
    Bull, D
    Crossley, B
    Goodill, A
    Green, J
    Hermon, C
    Key, T
    Langston, N
    Lewis, C
    Reeves, G
    Collins, R
    Doll, R
    Peto, R
    Mabuchi, K
    Preston, D
    Hannaford, P
    Kay, C
    Rosero-Bixby, L
    Gao, YT
    Jin, F
    Yuan, JM
    Wei, HY
    Yun, T
    Zhiheng, C
    Berry, G
    Cooper Booth, J
    Jelihovsky, T
    MacLennan, R
    Shearman, R
    Wang, QS
    Baines, CJ
    Miller, AB
    Wall, C
    Lund, E
    Stalsberg, H
    Shu, XO
    Zheng, W
    Katsouyanni, K
    Trichopoulou, A
    Trichopoulos, D
    Dabancens, A
    Martinez, L
    Molina, R
    Salas, O
    Alexander, FE
    Anderson, K
    Folsom, AR
    Hulka, BS
    Bernstein, L
    Enger, S
    Haile, RW
    Paganini-Hill, A
    Pike, MC
    Ross, RK
    Ursin, G
    Yu, MC
    Longnecker, MP
    Newcomb, P
    Bergkvist, L
    Uppsala University, Interfaculty Units, Centre for Clinical Research.
    Kalache, A
    Farley, TM
    Holck, S
    Meirik, O
    Alcohol, tobacco and breast cancer--collaborative reanalysis of individualdata from 53 epidemiological studies, including 58,515 women with breastcancer and 95,067 women without the disease.2002In: Br J Cancer, Vol. 87, p. 1234-45Article in journal (Refereed)
  • 24. Harris, H. R.
    et al.
    Bergkvist, Leif
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , Centre for Clinical Research, County of Västmanland.
    Wolk, A.
    Alcohol intake and mortality among women with invasive breast cancer2012In: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 106, no 3, p. 592-595Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Alcohol intake has consistently been associated with increased breast cancer incidence in epidemiological studies. However, the relation between alcohol and survival after breast cancer diagnosis is less clear.

    METHODS: We investigated whether alcohol intake was associated with survival among 3146 women diagnosed with invasive breast cancer in the Swedish Mammography Cohort. Alcohol consumption was estimated using a food frequency questionnaire. Cox proportional hazard models were used to calculate hazard ratios (HRs) and 95% confidence intervals (95% CIs).

    RESULTS: From 1987 to 2008 there were 385 breast cancer-specific deaths and 860 total deaths. No significant association was observed between alcohol intake and breast cancer-specific survival. Women who consumed 10 g per day (corresponding to approximately 0.75 to 1 drinks) or more of alcohol had an adjusted HR (95% CI) of breast cancer-specific death of 1.36 (0.82-2.26; p(trend) = 0.47) compared with non-drinkers. A significant inverse association was observed between alcohol and non-breast cancer deaths. Those who consumed 3.4-9.9 g per day of alcohol had a 33% lower risk of death compared with non-drinkers (95% CI 0.50-0.90; p(trend) = 0.04).

    CONCLUSION: Our findings suggest that alcohol intake up to approximately one small drink per day does not negatively impact breast cancer-specific survival and a half drink per day is associated with a decreased risk of mortality from other causes.

  • 25. Harris, H R
    et al.
    Bergkvist, Leif
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Wolk, A
    Coffee and black tea consumption and breast cancer mortality in a cohort of Swedish women2012In: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 107, no 5, p. 874-878Article in journal (Refereed)
    Abstract [en]

    Background:

    Coffee and black tea contain a mixture of compounds that have the potential to influence breast cancer risk and survival. However, epidemiologic data on the relation between coffee and black tea consumption and breast cancer survival are sparse.

    Methods:

    We investigated the association between coffee and black tea consumption and survival among 3243 women with invasive breast cancer in the Swedish Mammography Cohort. Intake was estimated using a food frequency questionnaire. Cox proportional hazard models were used to calculate hazard ratios (HRs) and 95% confidence intervals (95% CIs).

    Results:

    From 1987 to 2010 there were 394 breast cancer-specific deaths and 973 total deaths. Coffee and black tea were not associated with breast cancer-specific or overall mortality. Women consuming 4+ cups of coffee per day had a covariate and clinical characteristics-adjusted HR (95% CI) of death from breast cancer of 1.14 (0.71-1.83; ptrend=0.81) compared with those consuming <1 cup per day. Women consuming 2+ cups of black tea per day had a covariate and clinical characteristics-adjusted HR (95% CI) of death from breast cancer of 1.02 (0.67-1.55; ptrend=0.94) compared with non-tea drinkers. Caffeine was also not associated with breast cancer-specific (HR for top to bottom quartile=1.06; 95% CI=0.79-1.44; ptrend=0.71) or overall mortality.

    Conclusion:

    Our findings suggest that coffee, black tea, and caffeine consumption before breast cancer diagnosis do not influence breast cancer-specific and overall survival.

  • 26. Harris, H. R.
    et al.
    Bergkvist, Leif
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Wolk, A.
    Vitamin C intake and breast cancer mortality in a cohort of Swedish women2013In: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 109, no 1, p. 257-264Article in journal (Refereed)
    Abstract [en]

    Background: Vitamin C may influence cancer progression through its antioxidant properties. However, the evidence from observational epidemiologic studies on vitamin C intake and survival following breast cancer diagnosis is not consistent, and the safety of vitamin C supplements following breast cancer diagnosis has not been extensively studied. Methods: Using a food-frequency questionnaire we investigated whether vitamin C intake was associated with survival among 3405 women diagnosed with invasive breast cancer in the Swedish Mammography Cohort. Results: From 1987-2010, there were 1055 total deaths with 416 deaths from breast cancer. Women in the highest quartile of pre-diagnosis vitamin C intake had an adjusted HR (95% CI) of breast cancer death of 0.75 (0.57-0.99) compared with those in the lowest quartile (P-trend=0.03). There was a borderline significant association between vitamin C intake and total mortality (HR 0.84; 95% CI 0.71-1.00; P-trend=0.08). Among 717 breast cancer cases for whom post-diagnosis supplement use was available, there was no association between vitamin C supplement use (approximate to 1000 mg) and breast cancer-specific mortality (HR=1.06; 95% CI=0.52-2.17). Conclusion: Our findings suggest that dietary vitamin C intake before breast cancer diagnosis may be associated with breast cancer survival. In addition, post-diagnosis vitamin C supplementation at the level observed in our population was not associated with survival.

  • 27.
    Harris, Holly R.
    et al.
    Karolinska Inst, Natl Inst Environm Med, Div Nutr Epidemiol, SE-17177 Stockholm, Sweden.;Brigham & Womens Hosp, Obstet & Gynecol Epidemiol Ctr, 75 Francis St, Boston, MA 02115 USA..
    Bergkvist, Leif
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland. Cent Hosp Vasteras, Dept Surg, Vasteras, Sweden..
    Wolk, Alicja
    Karolinska Inst, Natl Inst Environm Med, Div Nutr Epidemiol, SE-17177 Stockholm, Sweden..
    Adherence to the World Cancer Research Fund/American Institute for Cancer Research recommendations and breast cancer risk2016In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 138, no 11, p. 2657-2664Article in journal (Refereed)
    Abstract [en]

    The World Cancer Research Fund/American Association for Cancer Research (WCRF/AICR) has published eight nutrition-related recommendations for the prevention of cancer. However, few prospective studies have examined these recommendations by breast cancer hormone receptor subtype and only one case-control study has included the dietary supplements recommendation in their evaluation. We investigated whether adherence to the WCRF/AICR cancer prevention recommendations was associated with breast cancer incidence, overall and by hormone receptor subtype, in the Swedish Mammography Cohort. Among 31,514 primarily postmenopausal women diet and lifestyle factors were assessed with a self-administered food frequency questionnaire. A score was constructed based on adherence to the recommendations for body fatness, physical activity, energy density, plant foods, animal foods, alcoholic drinks and dietary supplements (score range 0-7). Cox proportional hazard models were used to calculate hazard ratios (HRs) and 95% confidence intervals (95% CIs). During 15 years of follow-up 1,388 cases of breast cancer were identified. Women who met six to seven recommendations had a 51% decreased risk of breast cancer compared to women meeting only zero to two recommendations (95% CI = 0.35-0.70). The association between each additional recommendation met and breast cancer risk was strongest for the ER-positive/PR-positive subtype (HR = 0.86; 95% CI = 0.79-0.94), while for the ER-negative/PR-negative subtype the individual recommendations regarding plant and animal foods were most strongly associated with reduced risk. Our findings support that adherence to the WCRF/AICR recommendations reduces breast cancer risk in a population of primarily postmenopausal women. Promoting these recommendations to the public could help reduce breast cancer incidence.

  • 28. Harris, Holly R.
    et al.
    Bergkvist, Leif
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , Centre for Clinical Research, County of Västmanland.
    Wolk, Alicja
    Folate intake and breast cancer mortality in a cohort of Swedish women2012In: Breast Cancer Research and Treatment, ISSN 0167-6806, E-ISSN 1573-7217, Vol. 132, no 1, p. 243-250Article in journal (Refereed)
    Abstract [en]

    Folate may influence breast cancer development and progression through its role in one-carbon metabolism. However, epidemiologic data on the relation between folate and breast cancer survival are limited. We investigated whether dietary folate intake was associated with survival in 3,116 women diagnosed with breast cancer in the population-based Swedish Mammography Cohort. Participants completed a 67-item food frequency questionnaire in 1987. Cox proportional hazard models were used to calculate hazard ratios (HRs) and 95% confidence intervals (95% CIs) for death from breast cancer and death from any cause. During 25,716 person-years of follow-up from 1987 to 2008, there were 852 deaths with 381 breast cancer deaths. Dietary folate intake was inversely associated with breast cancer and overall mortality. Women in the highest quartile of folate intake had a multivariable HR (95% CI) of death from breast cancer of 0.78 (0.58-1.03) compared to those in the lowest quartile (P (trend) = 0.03). The corresponding HR (95% CI) for death from any cause was 0.79 (0.66-0.96; P (trend) = 0.004). The protective association between dietary folate intake and breast cancer death was strongest among those with ER-negative tumors (HR = 0.42; 95% = CI 0.22-0.79; P (trend) = 0.01) comparing the highest to lowest quartile. Our findings suggest that folate intake before breast cancer diagnosis may improve breast cancer and overall survival. While these findings need to be confirmed in future studies, they do offer assurance that dietary folate intake at the levels observed in our population does not unfavorably affect survival after breast cancer.

  • 29. Harris, Holly R.
    et al.
    Bergkvist, Leif
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Wolk, Alicja
    Selenium intake and breast cancer mortality in a cohort of Swedish women2012In: Breast Cancer Research and Treatment, ISSN 0167-6806, E-ISSN 1573-7217, Vol. 134, no 3, p. 1269-1277Article in journal (Refereed)
    Abstract [en]

    Selenium is an important cofactor in the production of antioxidant enzymes that may influence cancer progression. Selenium intake and cancer survival has not been extensively studied; however, selenium supplementation has been demonstrated to reduce cancer mortality in nutritional intervention trials. We investigated whether dietary selenium intake was associated with survival among 3,146 women diagnosed with invasive breast cancer in the population-based Swedish Mammography Cohort. Selenium intake before breast cancer diagnosis was estimated using a food frequency questionnaire completed in 1987. Cox proportional hazard models were used to calculate hazard ratios (HRs) and 95 % confidence intervals (95 % CIs) for death from breast cancer, non-breast cancer death, and death from any cause. During 28,172 person-years of follow-up from 1987 to 2009, there were 416 breast cancer-specific deaths and 964 total deaths. Dietary selenium intake was inversely associated with breast cancer-specific mortality and overall mortality. Women in the highest quartile of selenium intake had a multivariable HR (95 % CI) of death from breast cancer of 0.69 (0.52-0.92) compared with those in the lowest quartile (P (trend) = 0.009). The inverse association between dietary selenium intake and breast cancer death appeared strongest among women who had ever smoked (HR = 0.34; 95 % CI 0.14-0.83; P (trend) = 0.01) comparing the highest to lowest quartile. Our findings suggest that selenium intake before breast cancer diagnosis may improve breast cancer-specific survival and overall survival. However, these results may be limited to populations with low intakes of selenium.

  • 30.
    Høyer, Marie
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Caring Sciences.
    Nordin, Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Caring Sciences.
    Ahlgren, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Research and Development, Gävleborg.
    Bergkvist, Leif
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Lambe, Mats
    Regionalt Cancer Center Uppsala Örebro, Uppsala University Hospital; Department of medical epidemiology och biostatistics, Karolinska Institutet.
    Johansson, Birgitta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Lampic, Claudia
    Department of Neurobiology, Care Sciences and Society, Karolinska Institutet.
    Change in working time in a population-based cohort of patients with breast cancer2012In: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 30, no 23, p. 2853-2860Article in journal (Refereed)
    Abstract [en]

    Purpose:

    We examined changes in working time 16 months after a breast cancer diagnosis and identified factors associated with job discontinuation and/or decreased working time.

    Patients and Methods:

    This was a population-based cohort study with 735 patients identified in the Regional Breast Cancer Quality Register of Central Sweden. The study sample consisted of 505 women (age <63 years at diagnosis) who completed questionnaires at baseline and at follow-up (on average 4 and 16 months after diagnosis, respectively). Clinical register data and questionnaire data on sociodemographic factors were obtained at baseline. Self-reported work-related data were obtained at follow-up. Odds ratios were estimated by using logistic regression models.

    Results:

    Compared with prediagnosis working time, 72% reported no change in working time, 2% reported an increase, 15% reported a decrease, and 11% did not work at follow-up. Chemotherapy increased the likelihood (odds ratio [OR], 2.45; 95% CI, 1.38 to 4.34) of job discontinuation/decreased working time. Among chemotherapy recipients, associated factors included full-time work prediagnosis (OR, 3.25; 95% CI, 1.51 to 7.01), cancer-related work limitations (OR, 5.26; 95% CI, 2.30 to 12.03), and less value attached to work (OR, 3.69; 95% CI, 1.80 to 7.54). In the nonchemotherapy group, older age (OR, 1.09; 95% CI, 1.02 to 1.17) and less value attached to work (OR, 5.00; 95% CI, 2.01 to 12.45) were associated with the outcome.

    Conclusion:

    The majority of women treated for breast cancer returned to their prediagnosis working time. Chemotherapy and cancer-related work limitations are important factors to take into account in identifying women in need of support. Moreover, it is important to consider the woman’s own valuation of labor market participation.

  • 31.
    Johansson, Ann-Christin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , Centre for Clinical Research, County of Västmanland.
    Cornefjord, Michael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Bergkvist, Leif
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , Centre for Clinical Research, County of Västmanland.
    Öhrvik, John
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , Centre for Clinical Research, County of Västmanland.
    Linton, Steven J.
    Psychosocial stress factors among patients with lumbar disc herniation, scheduled for disc surgery in comparison with patients scheduled for arthroscopic knee surgery2007In: European spine journal, ISSN 0940-6719, E-ISSN 1432-0932, Vol. 16, no 7, p. 961-970Article in journal (Refereed)
    Abstract [en]

    Returning to work after disc surgery appears to be more heavily influenced by psychological aspects of work than by MR-identified morphological alterations. It is still not known whether psychosocial factors of importance for outcome after disc surgery are present preoperatively or develop in the postoperative phase. The aim of this study was to investigate the presence of work-related stress, life satisfaction and demanding life events, among patients undergoing first-time surgery for lumbar disc herniation in comparison with patients scheduled for arthroscopic knee surgery. Sixty-nine patients with disc herniation and 162 patients awaiting arthroscopy were included in the study, during the time period March 2003 to May 2005. Sixty-two percent of the disc patients had been on sick leave for an average of 7.8 months and 14 percent of the knee patients had been on sick leave for an average of 4.2 months. The psychosocial factors were investigated preoperatively using a questionnaire, which was a combination of the questionnaire of quality of work competence (QWC), life satisfaction (LiSat9) and life events as a modification of the social readjustment scale. There were no significant differences between the two groups in terms of work-related stress or the occurrence of demanding life events. The disc patients were significantly less satisfied with functions highly inter-related to pain and discomfort, such as present work situation, leisure-time, activities of daily living (ADL) function and sleep. Patients with disc herniation on sick leave were significantly less satisfied with their present work situation than knee patients on sick leave; this sub-group of patients with disc herniation also reported significantly higher expectations in relation to future job satisfaction than knee patients. The results indicate that psychosocial stress is not more pronounced preoperatively in this selected group of disc patients, without co-morbidity waiting for first-time disc surgery, than among knee patients awaiting arthroscopy. It was notable that the disc patients had high expectations in terms of improved job satisfaction after treatment by surgery.

  • 32.
    Johansson, Ann-Christin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Gunnarsson, Lars-Gunnar
    Linton, Steven J.
    Bergkvist, Leif
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Stridsberg, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemical endocrinology.
    Nilsson, Olle
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Cornefjord, Michael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Pain, disability and coping reflected in the diurnal cortisol variability in patients scheduled for lumbar disc surgery2008In: European Journal of Pain, ISSN 1090-3801, E-ISSN 1532-2149, Vol. 12, no 5, p. 633-640Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    Symptoms of lumbar disc herniation can be induced by both mechanical compression of the nerve roots and by biochemical irritants from the disc tissues. Proinflammatory cytokines, as well as stress are potent stimulators of the hypothalamic-pituitary-adrenal axis, reflected in enhanced release of cortisol from the adrenal cortex. Altered cortisol production is also associated to behaviour and coping patterns. The aim of the present study was to explore the relation between pain, physical function, psychosocial factors and quality of life to the diurnal cortisol variability, in patients with lumbar disc herniation.

    METHOD:

    This study had a cross-sectional design. Forty-two patients with lumbar disc herniation, verified by magnetic resonance imaging and a clinical examination by an orthopaedic surgeon, were included in the study. All patients were scheduled for disc surgery. The diurnal cortisol variability was examined before surgery. The patients were dichotomised into two groups based on low or high diurnal cortisol variability. Pain, disability, work related stress, quality of life, coping and fear avoidance beliefs, were estimated by standardised questionnaires.

    RESULTS:

    The low diurnal cortisol variability group was distinguished by a higher median score regarding leg pain at activity and significantly more disability (p<0.05). The patients with a low diurnal cortisol variability had significantly lower coping self-statement scores, but higher pain coping catastrophising scores (p<0.05).

    CONCLUSION:

    Patients with lumbar disc herniation and a low diurnal cortisol variability had lower physical function, perceived lower possibilities of influencing their pain, and were more prone to catastrophise than patients with lumbar disc herniation and a high diurnal cortisol variability.

  • 33.
    Johansson, Ann-Christin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Linton, Steven J.
    Rosenblad, Andreas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Bergkvist, Leif
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Nilsson, Olle
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    A prospective study of cognitive behavioural factors as predictors of pain, disability and quality of life one year after lumbar disc surgery2010In: Disability and Rehabilitation, ISSN 0963-8288, E-ISSN 1464-5165, Vol. 32, no 7, p. 521-529Article in journal (Refereed)
    Abstract [en]

    Purpose

    The primary aim of this study was to analyse the predictive value of cognitive and behavioural factors, in relation to pain, disability and quality of life (QoL) one year after lumbar disc surgery.

    Method

    The study design was prospective. Fifty-nine patients scheduled for first time lumbar disc surgery were included. Pain, disability, QoL, coping, fear avoidance beliefs, expected outcome and sick leave were assessed preoperatively and 12 months after surgery. Multiple backward stepwise logistic regression analyses were performed to study the contribution of the preoperatively measured independent behavioural/cognitive factors (coping, fear avoidance beliefs and assessed chance to return to work within 3 months) to the dependent variables pain, disability and quality of life at 12 months after surgery.

    Results

    Low expectations on work return within 3 months after surgery was significantly predictive for residual leg pain, odds ratio (OR) = 8.2, back pain, OR = 9.7, disability, OR = 13.8 and sick leave, OR = 19.5. Low QoL, was best predicted by preoperatively high scores on fear avoidance beliefs OR = 6.6 and being a woman OR = 6.0. The regression model explained 26-40% of the variance in pain, disability, QoL and sick leave.

    Conclusions

    Eliciting patients' expectations on work return after surgery could contribute to early identification of those who run the risk of developing long-term disability and sick-leave.

  • 34. Julin, Bettina
    et al.
    Wolk, Alicja
    Bergkvist, Leif
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , Centre for Clinical Research, County of Västmanland.
    Bottai, Matteo
    Akesson, Agneta
    Dietary Cadmium Exposure and Risk of Postmenopausal Breast Cancer: A Population-Based Prospective Cohort Study2012In: Cancer Research, ISSN 0008-5472, E-ISSN 1538-7445, Vol. 72, no 6, p. 1459-1466Article in journal (Refereed)
    Abstract [en]

    The ubiquitous food contaminant cadmium has features of an estrogen mimetic that may promote the development of estrogen-dependent malignancies, such as breast cancer. However, no prospective studies of cadmium exposure and breast cancer risk have been reported. , We examined the association between dietary cadmium exposure (at baseline, 1987) and the risk of overall and estrogen receptor (ER)-defined (ER+ or ER-) breast cancer within a population-based prospective cohort of 55,987 postmenopausal women. During an average of 12.2 years of follow-up, 2,112 incident cases of invasive breast cancer were ascertained (1,626 ER+ and 290 ER-). After adjusting for confounders, including consumption of whole grains and vegetables (which account for 40% of the dietary exposure, but also contain putative anticarcinogenic phytochemicals), dietary cadmium intake was positively associated with overall breast cancer tumors, comparing the highest tertile with the lowest [rate ratio (RR), 1.21; 95% confidence interval (CI), 1.07-1.36; P-trend = 0.02]. Among lean and normal weight women, statistically significant associations were observed for all tumors (RR, 1.27; 95% CI, 1.07-1.50) and for ER+ tumors (RR, 125; 95% CI, 1.03-1.52) and similar, but not statistically significant associations were found for ER- tumors (RR, 1.22; 95% CI, 0.76-1.93). The risk of breast cancer increased with increasing cadmium exposure similarly within each textile of whole grain/vegetable consumption and decreased with increasing consumption of whole grain/vegetables within each tertile of cadmium exposure (P-interaction = 0.73). Overall, these results suggest a role for dietary cadmium in postmenopausal breast cancer development.

  • 35.
    Karakatsanis, A.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Oloffson, H.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Bergkvist, Leif A.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Abdsaleh, Shahin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science.
    Sund, M.
    Warnberg, F.
    How to avoid unnecessary sentinel node biopsy in patients with ductal cancer in situ2015In: Breast, ISSN 0960-9776, E-ISSN 1532-3080, Vol. 24, p. S133-S134Article in journal (Other academic)
  • 36.
    Karakatsanis, Andreas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Christiansen, Peer Michael
    Aarhus Univ Hosp, Randers Reg Hosp, Dept Surg, Breast Unit, DK-8000 Aarhus, Denmark..
    Fischer, Lone
    Aarhus Univ Hosp, Randers Reg Hosp, Dept Surg, Breast Unit, DK-8000 Aarhus, Denmark..
    Hedin, Christina
    Linkoping Univ Hosp, Dept Surg, Breast Unit, S-58185 Linkoping, Sweden..
    Pistioli, Lida
    Linkoping Univ Hosp, Dept Surg, Breast Unit, S-58185 Linkoping, Sweden..
    Sund, Malin
    Dept Surg & Perioperat Sci, Umea, Sweden..
    Rasmussen, Nils Ryegaard
    SVS, Dept Surg, Breast Unit, Esbjerg, Denmark..
    Jornsgard, Hjordis
    SVS, Dept Surg, Breast Unit, Esbjerg, Denmark..
    Tegnelius, Daniel
    Univ Orebro, Dept Surg, Breast Unit, SE-70182 Orebro, Sweden..
    Eriksson, Staffan
    Vastmanland Cty Hosp, Dept Surg, Vasteras, Sweden..
    Daskalakis, Kosmas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Wärnberg, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Markopoulos, Christos J.
    Univ Athens, Sch Med, Athens 11528, Greece..
    Bergkvist, Leif
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland. Vastmanland Cty Hosp, Dept Surg, Vasteras, Sweden..
    The Nordic SentiMag trial: a comparison of super paramagnetic iron oxide (SPIO) nanoparticles versus Tc-99 and patent blue in the detection of sentinel node (SN) in patients with breast cancer and a meta-analysis of earlier studies2016In: Breast Cancer Research and Treatment, ISSN 0167-6806, E-ISSN 1573-7217, Vol. 157, no 2, p. 281-294Article in journal (Refereed)
    Abstract [en]

    The aim of the study is to compare the efficacy of SPIO as a tracer in sentinel node biopsy (SNB) in breast cancer with Tc and patent blue in a multicentre prospective study and perform a meta-analysis of all published studies. It also aims to follow skin discoloration after SPIO injection and describe when and how it resolves. Totally 206 patients with early breast cancer were recruited. Tc and patent blue were administered in standard fashion. Patients were injected with SPIO (Sienna+) preoperatively. SNB was performed and detection rates were recorded for both methods. Skin discoloration was followed and documented postoperatively. Data extraction and subsequent meta-analysis of all previous studies were also performed. SN detection rates were similar between standard technique succeeded and SPIO both per patient (97.1 vs. 97.6 %, p = 0.76) as well as per node (91.3 vs. 93.3 %, p = 0.34), something which was not affected by the presence of malignancy. Concordance rates were also consistently high (98.0 % per patient and 95.9 % per node). Discoloring was present in 35.5 % of patients postoperatively, almost exclusively in breast conservation. It fades slowly and is still detectable in 8.6 % of patients after 15 months. Meta-analysis depicted similar detection rates (p = 0.71) and concordance rates (p = 0.82) per patient. However, it seems that SPIO is characterized by higher nodal retrieval (p < 0.001). SPIO is an effective method for the detection of SN in patients with breast cancer. It is comparable to the standard technique and seems to simplify logistics. Potential skin discoloration is something of consideration in patients planned for breast conservation.

  • 37.
    Karakatsanis, Andreas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Daskalakis, Kosmas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Stålberg, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Olofsson, H
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Andersson, Y
    Department of Surgery, Västmanlands County Hospital, Västerås, Sweden.
    Eriksson, S
    Department of Surgery, Västmanlands County Hospital, Västerås, Sweden.
    Bergkvist, Leif
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Wärnberg, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Superparamagnetic iron oxide nanoparticles as the sole method for sentinel node biopsy detection in patients with breast cancer2017In: British Journal of Surgery, ISSN 0007-1323, E-ISSN 1365-2168, Vol. 104, no 12, p. 1675-1685Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Sentinel node biopsy (SNB) using superparamagnetic iron oxide (SPIO) nanoparticles is a novel method in breast cancer. Several studies have verified the non-inferiority of SPIO compared with the standard use of radioisotope (99m) Tc with or without blue dye. The aim of the MONOS study presented here was to evaluate the use of SPIO as a sole tracer and the efficacy of tracer injection in the preoperative setting.

    METHODS: This prospective cohort study was carried out in two hospitals, one using (99m) Tc and the other SPIO. (99m) Tc was injected in the morning of the day of surgery or the day before. SPIO was either injected before surgery in the outpatient clinic or 1 h before the operation.

    RESULTS: A total of 338 consecutive patients with breast cancer underwent 343 procedures; SPIO nanoparticles were used in 184 procedures and (99m) Tc-labelled tracer in 159. Detection rates for SPIO and (99m) Tc were 95·6 and 96·9 per cent respectively (P = 0·537). All nodes with SPIO uptake were coloured brown. Fewer nodes were retrieved with SPIO (mean 1·35 versus 1·89), regardless of whether blue dye was used (P < 0·001). Preoperative SPIO injection (58·7 per cent of procedures), a median of 16 (range 2-27) days before the procedure, was associated with a better tracer-specific detection rate (95·3 versus 86 per cent; P = 0·031) and retrieval of more nodes (mean 1·43 versus 1·03; P < 0·001) than perioperative administration. Skin staining was present in 39·9 per cent of patients, and was related to breast-conserving surgery and periareolar injection.

    CONCLUSION: The use of SPIO alone is a safe alternative, with results comparable to those of the standard dual technique using (99m) Tc and blue dye. The efficacy of injection in the preoperative setting simplifies logistics and improves performance. Skin staining can be prevented by a deeper peritumoral injection.

  • 38.
    Karakatsanis, Andreas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Olofsson, H. M.
    Eriksson, S.
    Andersson, Y.
    Bergkvist, Leif A.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Mohammed, I.
    Sundqvist, M.
    Abdsaleh, Shahin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Bagge, R. Olofsson
    Sund, M.
    Wärnberg, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    SentiNot: A way to avoid sentinel node biopsy (SNB) in patients with a preoperative diagnosis of ductal cancer in situ (DCIS)2017In: Cancer Research, ISSN 0008-5472, E-ISSN 1538-7445, Vol. 77Article in journal (Refereed)
  • 39.
    Karakatsanis, Andreas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Olofsson, H
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Stålberg, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Bergkvist, Leif
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Abdsaleh, S
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Wärnberg, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Simplifying Logistics and Avoiding the Unnecessary in Patients with Breast Cancer Undergoing Sentinel Node Biopsy. A Prospective Feasibility Trial of the Preoperative Injection of Super Paramagnetic Iron Oxide Nanoparticles2018In: Scandinavian Journal of Surgery, ISSN 1457-4969, E-ISSN 1799-7267, Vol. 107, no 2, p. 130-137Article in journal (Refereed)
    Abstract [en]

    PURPOSE: Sentinel node is routinely localized with the intraoperative use of a radioactive tracer, involving challenging logistics. Super paramagnetic iron oxide nanoparticle is a non-radioactive tracer with comparable performance that could allow for preoperative localization, would simplify the procedure, and possibly be of value in axillary mapping before neoadjuvant treatment. The current trial aimed to determine the a priori hypothesis that the injection of super paramagnetic iron oxide nanoparticles in the preoperative period for the localization of the sentinel node is feasible.

    METHODS: This is a prospective feasibility trial, conducted from 9 September 2014 to 22 October 2014 at Uppsala University Hospital. In all, 12 consecutive patients with primary breast cancer planned for resection of the primary and sentinel node biopsy were recruited. Super paramagnetic iron oxide nanoparticles were injected in the preoperative visit in the outpatient clinic. The radioactive tracer (99mTc) and the blue dye were injected perioperatively in standard fashion. A volunteer was injected with super paramagnetic iron oxide nanoparticles to follow the decline in the magnetic signal in the sentinel node over time. The primary outcome was successful sentinel node detection.

    RESULTS: Super paramagnetic iron oxide nanoparticles' detection after preoperative injection (3-15 days) was successful in all cases (100%). In the volunteer, axillary signal was presented for 4 weeks. No adverse effects were noted. Conclusion and relevance: Preoperative super paramagnetic iron oxide nanoparticles' injection is feasible and leads to successful detection of the sentinel node. That may lead to simplified logistics as well as the identification, sampling, and marking of the sentinel node in patients planned for neoadjuvant treatment.

  • 40. Koushik, Anita
    et al.
    Spiegelman, Donna
    Albanes, Demetrius
    Anderson, Kristin E
    Bernstein, Leslie
    van den Brandt, Piet A
    Bergkvist, Leif
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    English, Dallas R
    Freudenheim, Jo L
    Fuchs, Charles S
    Genkinger, Jeanine M
    Giles, Graham G
    Goldbohm, R Alexandra
    Horn-Ross, Pamela L
    Männistö, Satu
    McCullough, Marjorie L
    Millen, Amy E
    Miller, Anthony B
    Robien, Kim
    Rohan, Thomas E
    Schatzkin, Arthur
    Shikany, James M
    Stolzenberg-Solomon, Rachael Z
    Willett, Walter C
    Wolk, Alicja
    Ziegler, Regina G
    Smith-Warner, Stephanie A
    Intake of fruits and vegetables and risk of pancreatic cancer in a pooled analysis of 14 cohort studies2012In: American Journal of Epidemiology, ISSN 0002-9262, E-ISSN 1476-6256, Vol. 176, no 5, p. 373-386Article in journal (Refereed)
    Abstract [en]

    Fruit and vegetable intake may protect against pancreatic cancer, since fruits and vegetables are rich in potentially cancer-preventive nutrients. Most case-control studies have found inverse associations between fruit and vegetable intake and pancreatic cancer risk, although bias due to reporting error cannot be ruled out. In most prospective studies, inverse associations have been weaker and imprecise because of small numbers of cases. The authors examined fruit and vegetable intake in relation to pancreatic cancer risk in a pooled analysis of 14 prospective studies from North America, Europe, and Australia (study periods between 1980 and 2005). Relative risks and 2-sided 95% confidence intervals were estimated separately for the 14 studies using the Cox proportional hazards model and were then pooled using a random-effects model. Of 862,584 men and women followed for 7-20 years, 2,212 developed pancreatic cancer. The pooled multivariate relative risks of pancreatic cancer per 100-g/day increase in intake were 1.01 (95% confidence interval (CI): 0.99, 1.03) for total fruits and vegetables, 1.01 (95% CI: 0.99, 1.03) for total fruits, and 1.02 (95% CI: 0.99, 1.06) for total vegetables. Associations were similar for men and women separately and across studies. These results suggest that fruit and vegetable intake during adulthood is not associated with a reduced pancreatic cancer risk.

  • 41. Larsson,
    et al.
    Bergkvist,
    Uppsala University, Interfaculty Units, Centre for Clinical Research.
    Wolk,
    Processed meat consumption, dietary nitrosamines and stomach cancer risk in a cohort of Swedish women.2006In: Int J Cancer, ISSN 0020-7136Article in journal (Refereed)
  • 42. Larsson,
    et al.
    Giovannucci,
    Bergkvist, Leif
    Uppsala University, Interfaculty Units, Centre for Clinical Research.
    Wolk,
    Aspirin and nonsteroidal anti-inflammatory drug use and risk of pancreatic: a meta-analysis.2006In: Cancer Epidemiol Biomarkers Prev, ISSN 1055-9965, Vol. 15, no 12, p. 2561-4Article in journal (Refereed)
  • 43. Larsson, S C
    et al.
    Giovannucci, E
    Bergkvist, L
    Uppsala University, Interfaculty Units, Centre for Clinical Research.
    Wolk, A
    Whole grain consumption and risk of colorectal cancer: a population-based cohort of 60,000 women.2005In: Br J Cancer, ISSN 0007-0920, Vol. 92, no 9, p. 1803-7Article in journal (Refereed)
  • 44. Larsson, S C
    et al.
    Permert, J
    Håkansson, N
    Näslund, I
    Bergkvist, L
    Uppsala University, Interfaculty Units, Centre for Clinical Research.
    Wolk, A
    Overall obesity, abdominal adiposity, diabetes and cigarette smoking in relation to the risk of pancreatic cancer in two Swedish population-based cohorts.2005In: Br J Cancer, ISSN 0007-0920, Vol. 93, no 11, p. 1310-5Article in journal (Refereed)
  • 45. Larsson, S.
    et al.
    Rutegård, J.
    Bergkvist, Leif
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , Centre for Clinical Research, County of Västmanland.
    Wolk, A.
    Physical activity, obesity, and risk of colon and rectal cancer in a cohort of Swedish men2006In: European Journal of Cancer, ISSN 0959-8049, E-ISSN 1879-0852, Vol. 42, no 15, p. 2590-2597Article in journal (Refereed)
    Abstract [en]

    We investigated the association between physical activity and colorectal cancer risk in a cohort of Swedish men. Information on physical activity was obtained at baseline in 1997 with a self-administered questionnaire from 45,906 men who were cancer-free at enrollment. During a mean follow-up of 7.1 years, 496 cases of colorectal cancer occurred.. Leisure-time physical activity was inversely associated with colorectal cancer risk; the multivariate hazard ratio (HR) for 60 min or more per day of leisure-time physical activity compared with less than 10 min per day was 0.57 (95% CI 0.41-0.79; P for trend = 0.001). Results were similar for colon (HR = 0.56; 95% CI 0.37-0.83) and rectal cancer (HR = 0.59; 95% CI 0.34-1.02). Home/housework activity was inversely associated with colon cancer risk (HR = 0.68; 95% CI 0.48-0.96). No association was observed for work/occupational activity. These results support a role of physical activity in reducing the risk of colon and rectal cancer.

  • 46. Larsson, Susanna C
    et al.
    Bergkvist, Leif
    Uppsala University, Interfaculty Units, Centre for Clinical Research.
    Giovannucci, Edward
    Wolk, Alicja
    Coffee consumption and incidence of colorectal cancer in two prospective cohort studies of Swedish women and men.2006In: Am J Epidemiol, ISSN 0002-9262, Vol. 163, no 7, p. 638-44Article in journal (Refereed)
  • 47. Larsson, Susanna C.
    et al.
    Bergkvist, Leif
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , Centre for Clinical Research, County of Västmanland.
    Näslund, Ingmar
    Rutegård, Jörgen
    Wolk, Alicja
    Vitamin A, retinol, and carotenoids and the risk of gastric cancer: a prospective cohort study2007In: American Journal of Clinical Nutrition, ISSN 0002-9165, E-ISSN 1938-3207, Vol. 85, no 2, p. 497-503Article in journal (Refereed)
    Abstract [en]

    Background: Vitamin A may influence gastric carcinogenesis through its essential role in controlling cell proliferation and differentiation. However, epidemiologic studies of vitamin A, retinol (preformed vitamin A), and provitamin A carotenoids in relation to the risk of gastric cancer have documented inconsistent results. Objective: The objective of the study was to examine the associations between intakes of vitamin A, retinol, and specific carotenoids and the risk of gastric cancer in a prospective population-based cohort study of Swedish adults. Design: The study cohort consisted of 82 002 Swedish adults aged 45-83 y who had completed a food-frequency questionnaire in 1997. The participants were followed through June 2005. Results: During a mean 7.2-y follow-up, 139 incident cases of gastric cancer were diagnosed. High intakes of vitamin A and retinol from foods only (dietary intake) and from foods and supplements combined (total intake) and of dietary α-carotene and β-carotene were associated with a lower risk of gastric cancer. The multivariate relative risks for the highest versus lowest quartiles of intake were 0.53 (95% CI: 0.32,0.89; P for trend = 0.02) for total vitamin A, 0.56 (95% CI: 0.33, 0.95; P for trend = 0.05) for total retinol, 0.50 (95% CI: 0.30,0.83; P for trend = 0.03) for a-carotene, and 0.55 (95% CI: 0.32, 0.94; P for trend = 0.07) for β-carotene. No significant associations were found for β-cryptoxanthin, lutein and zeaxanthin, or lycopene intake. Conclusion: High intakes of vitamin A, retinol, and provitamin A carotenoids may reduce the risk of gastric cancer.

  • 48. Larsson, Susanna C
    et al.
    Bergkvist, Leif
    Uppsala University, Interfaculty Units, Centre for Clinical Research.
    Rutegård, Jörgen
    Giovannucci, Edward
    Wolk, Alicja
    Calcium and dairy food intakes are inversely associated with colorectal cancer risk in the Cohort of Swedish Men.2006In: Am J Clin Nutr, ISSN 0002-9165, Vol. 83, no 3, p. 667-73; quiz 728Article in journal (Refereed)
  • 49. Larsson, Susanna C.
    et al.
    Bergkvist, Leif
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , Centre for Clinical Research, County of Västmanland.
    Wolk, Alicja
    Consumption of sugar and sugar-sweetened foods and the risk of pancreatic cancer in a prospective study2006In: American Journal of Clinical Nutrition, ISSN 0002-9165, E-ISSN 1938-3207, Vol. 84, no 5, p. 1171-1176Article in journal (Refereed)
    Abstract [en]

    Background: Emerging evidence indicates that hyperglycemia and hyperinsulinemia may be implicated in the development of pancreatic cancer. Frequent consumption of sugar and high-sugar foods may increase the risk of pancreatic cancer by inducing frequent postprandial hyperglycemia, increasing insulin demand, and decreasing insulin sensitivity.

    Objective: The objective of the study was to examine prospectively the association of the consumption of added sugar (ie, sugar added to coffee, tea, cereals, etc) and of high-sugar foods with the risk of pancreatic cancer in a population-based cohort study of Swedish women and men.

    Design: A food-frequency questionnaire was completed in 1997 by 77 797 women and men aged 45-83 y who had no previous diagnosis of cancer or history of diabetes. The participants were followed through June 2005.

    Results: During a mean follow-up of 7.2 y, we identified 131 incident cases of pancreatic cancer. The consumption of added sugar, soft drinks, and sweetened fruit soups or stewed fruit was positively associated with the risk of pancreatic cancer. The multivariate hazard ratios for the highest compared with the lowest consumption categories were 1.69 (95% CI: 0.99, 2.89; P for trend = 0.06) for sugar, 1.93 (1.18, 3.14; P for trend = 0.02) for soft drinks, and 1.51 (0.97, 2.36; P for trend 0.05) for sweetened fruit soups or stewed fruit.

    Conclusion: High consumption of sugar and high-sugar foods may be associated with a greater risk of pancreatic cancer.

  • 50. Larsson, Susanna C.
    et al.
    Bergkvist, Leif
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , Centre for Clinical Research, County of Västmanland.
    Wolk, Alicja
    Fruit and vegetable consumption and incidence of gastric cancer: a prospective study2006In: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 15, no 10, p. 1998-2001Article in journal (Refereed)
    Abstract [en]

    Background: Whether fruit and vegetable consumption may confer protection from gastric cancer remains controversial.

    Methods: We prospectively investigated the association between consumption of fruits and vegetables and the incidence of gastric cancer among participants from two population-based cohort studies: 36,664 women in the Swedish Mammography Cohort and 45,338 men in the Cohort of Swedish Men. Participants completed a food-frequency questionnaire in 1997 and were followed up for cancer incidence through June 2005. Cox proportional hazards models were used to estimate multivariate hazard ratios (HR) and 95% confidence intervals (95% CI).

    Results: During a mean follow-up of 7.2 years, we ascertained 139 incident cases of gastric cancer. Vegetable consumption was inversely associated with risk of gastric cancer, whereas no significant association was observed for fruit consumption. After controlling for age and other risk factors, women and men who consumed >= 2.5 servings/d of vegetables had a HR of 0.56 (95% CI, 0.34-0.93) for developing gastric cancer compared with those who consumed < 1 serving/d. The respective HR for fruit consumption was 0.86 (95% CI, 0.52-1.43). Among specific subgroups of vegetables, consumption of green leafy vegetables and root vegetables was inversely associated with risk of gastric cancer, the multivariate HRs comparing >= 3 servings/wk with < 0.5 serving/wk were 0.64 (95% CI, 0.42-0.99) for green leafy vegetables and 0.43 (95% CI, 0.27-0.69) for root vegetables.

    Conclusions: Frequent consumption of vegetables may reduce the risk of gastric cancer.

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