Publications by authors named "Jan-Erik Johansson"

118 Publications

Impact of cancer screening on metastasis: A prostate cancer case study.

J Med Screen 2021 Feb 9:969141321989738. Epub 2021 Feb 9.

Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.

Background: Trials of cancer screening present results in terms of deaths prevented, but metastasis is also a key endpoint that screening seeks to prevent. We developed a framework for projecting overall (de novo and progressive) metastases prevented in a screening trial using prostate cancer screening as a case study.

Methods: Mechanistic simulation model in which screening shifts a fraction of cases that would be metastatic at diagnosis to being non-metastatic. This shift increases the incidence of non-overdiagnosed, organ-confined cases. We use estimates of the risk of metastatic progression for these cases to project how many progress to metastasis after diagnosis and tally the projected de novo and progressive metastatic cases with and without screening. We use data on stage shift from the European Randomized Study of Screening for Prostate Cancer (ERSPC) and data on the risk of metastatic progression from the Scandinavian Prostate Cancer Group-4 trial. We estimate the relative risk and absolute risk reductions in metastatic disease at diagnosis and compare these with reductions in overall metastases.

Results: Assuming no effect of screening beyond initial stage shift at diagnosis, the model projects a 43% reduction in metastasis at diagnosis but a 22% reduction in the cumulative probability of metastasis over 12 years in favor of screening. These results are consistent with the empirical findings from the ERSPC.

Conclusion: Any reduction in metastatic disease at diagnosis under screening is likely to be an overly optimistic predictor of the impact of screening on overall metastasis and disease-specific mortality.
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http://dx.doi.org/10.1177/0969141321989738DOI Listing
February 2021

Outcome of allogeneic haematopoietic stem cell transplantation in myeloproliferative neoplasm, unclassifiable: a retrospective study by the Chronic Malignancies Working Party of the EBMT.

Br J Haematol 2020 08 28;190(3):437-441. Epub 2020 Feb 28.

Université de Lille, Inserm, CHU Lille. INSERM, Infinite, U1286, Lille, France.

Myeloproliferative Neoplasm (MPN), unclassifiable (MPN-U) is a heterogeneous disease with regards to both clinical phenotype and disease course. Patients may initially be asymptomatic or present with leucocytosis or thrombocytosis, anaemia, progressive splenomegaly, constitutional symptom, thromboses or accelerated/blastic phase disease. Treatment strategies are variable and there are no widely accepted consensus management guidelines for MNU-U. Allogeneic Haematopoietic Cell Transplantation (allo-HCT) remains the only curative strategy yet outcomes, to date, are not well defined. We hereby report on the largest retrospective study of patients with MPN-U undergoing allo-HCT, highlighting the potentially curative role and providing clinicians with robust engraftment, GvHD and outcome data to facilitate patient discussion.
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http://dx.doi.org/10.1111/bjh.16537DOI Listing
August 2020

Microbial changes in relation to oral mucositis in autologous hematopoietic stem cell transplantation recipients.

Sci Rep 2019 11 15;9(1):16929. Epub 2019 Nov 15.

Department of Preventive Dentistry, Academic Centre for Dentistry Amsterdam, University of Amsterdam and Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.

The aim of this prospective, two center study was to investigate the dynamics of the microbial changes in relation to the development of ulcerative oral mucositis in autologous SCT (autoSCT) recipients. Fifty-one patients were diagnosed with multiple myeloma and treated with high-dose melphalan followed by autoSCT. They were evaluated before, three times weekly during hospitalization, and three months after autoSCT. At each time point an oral rinse was collected and the presence or absence of ulcerative oral mucositis (UOM) was scored (WHO scale). Oral microbiome was determined by using 16S rRNA amplicon sequencing and fungal load by qPCR. Twenty patients (39%) developed UOM. The oral microbiome changed significantly after autoSCT and returned to pre-autoSCT composition after three months. However, changes in microbial diversity and similarity were more pronounced and rapid in patients who developed UOM compared to patients who did not. Already before autoSCT, different taxa discriminated between the 2 groups, suggesting microbially-driven risk factors. Samples with high fungal load (>0.1%) had a significantly different microbial profile from samples without fungi. In conclusion, autoSCT induced significant and reversible changes in the oral microbiome, while patients who did not develop ulcerative oral mucositis had a more resilient microbial ecosystem.
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http://dx.doi.org/10.1038/s41598-019-53073-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6858439PMC
November 2019

Quality of Life after Radical Prostatectomy or Watchful Waiting With or Without Androgen Deprivation Therapy: The SPCG-4 Randomized Trial.

Eur Urol Oncol 2018 06 15;1(2):134-142. Epub 2018 May 15.

Department of Surgical Sciences, University Hospital of Uppsala, Uppsala, Sweden.

Background: Men with prostate cancer experience adjuvant androgen deprivation therapy (ADT) differently.

Objective: To evaluate the effect of ADT on quality of life (QoL), patients' experience of clinical check-ups, and differences in cancer information as explanatory factors.

Design, Setting, And Participants: A study-specific questionnaire was sent to all men randomized in the SPCG-4 trial to radical prostatectomy (RP) or watchful waiting (WW) still alive (400/695) and a control group of 281 men.

Intervention: ADT.

Outcome Measurements And Statistical Analysis: Self-assessed QoL, worry at clinical check-ups, and amount of information received. Estimated relative risks with associated 95% confidence intervals (CI) for risk comparisons between groups using a log-binomial regression.

Results And Limitations: The SPCG-4 men had median follow-up of 12.2 yr and median age of 77.0 yr; 26% in the RP group and 40% in the WW group received ADT treatment. High QoL for men without ADT was 36% for the RP group, 44% for the WW group, and 45% for the control group. High QoL for men with ADT was 30% for the RP group and 20% for the WW group. Among men with ADT, those in the WW group received significantly less information about the disease than men in the RP group. Receiving no or little information about prostate cancer was reported by 17% of patients in the RP group and 39% in the WW group among men receiving ADT (relative risk 0.44, 95% CI 0.22-0.89). At clinical check-ups, men treated with ADT had significantly higher levels of worry, regardless of study group, than men without ADT. Limitations include the lack of longitudinal data and a low number of men receiving ADT in the RP group.

Conclusions: Men on WW without ADT reported high QoL comparable to that for men without prostate cancer. ADT treatment in the WW group was associated with the lowest scores for all psychological parameters, and these men reported that they were least informed about prostate cancer and its consequences.

Patient Summary: Good communication and information from caregivers are associated with less negative psychological effects at prostate cancer progression.
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http://dx.doi.org/10.1016/j.euo.2018.03.003DOI Listing
June 2018

Apical periodontitis as potential source of infection in patients with lymphoma treated with chemotherapy.

Clin Oral Investig 2020 Jan 1;24(1):133-140. Epub 2019 May 1.

Department of Oral Medicine and Pathology, Institute of Odontology, The Sahlgrenska Academy, University of Gothenburg, Box 450, 405 30, Gothenburg, Sweden.

Objectives: To investigate signs of infection and infection-related complications of apical periodontitis (AP) in patients who underwent chemotherapy for lymphoma.

Materials And Methods: Data were collected retrospectively from the dental and medical records of patients receiving chemotherapy for lymphoma. Based on the findings from a dental evaluation made in conjunction with chemotherapy, the patients were divided into two groups, patients with or without teeth with AP.

Results: Eighty-six of the 213 patients had one or more teeth with AP and received no planned dental treatment for this condition, while 127 patients had no AP-affected teeth. During chemotherapy, seven patients (8%) developed local symptoms related to teeth with AP, while no patients in the control group developed symptoms of AP. No significant differences were found with respect to the administration of antibiotics related to dental infection or hospital admission events due to fever or infection, between the group with AP and the group without AP.

Conclusions: AP is a common finding and exacerbation seems more common in patients diagnosed with chronic AP than in patients without chronic AP. The presence of chronic AP in patients treated with chemotherapy for lymphoma is not linked to additional medical complications that require hospital admission owing to fever/infection.

Clinical Relevance: Knowledge regarding infection-related complications of AP in patients with lymphoma treated with chemotherapy will guide clinical decision-making by identifying those patients who warrant treatment. This will allow dental interventions to be postponed until completion of chemotherapy, without serious medical complications. The results of this study serve as a basis for larger prospective studies.
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http://dx.doi.org/10.1007/s00784-019-02909-wDOI Listing
January 2020

Cryotherapy as prophylaxis against oral mucositis after high-dose melphalan and autologous stem cell transplantation for myeloma: a randomised, open-label, phase 3, non-inferiority trial.

Bone Marrow Transplant 2019 09 4;54(9):1482-1488. Epub 2019 Feb 4.

Department of Oral Medicine and Pathology, Institute of Odontology, The Sahlgrenska Academy at Göteborg University, Göteborg, Sweden.

The conditioning therapy used in connection with haematopoietic stem cell transplantation (HSCT) can induce painful oral mucositis, which has negative impacts on patient quality of life and survival, as well as on health-care costs. While cooling of the oral mucosa (cryotherapy) is regarded as standard prophylaxis against oral mucositis, the long duration of the treatment affects compliance owing to side effects. In this prospective, randomised trial, 94 patients (62 males/32 females; median age 59 years, range 34-69) with a diagnosis of myeloma who were undergoing autologous HSCT were randomised 1:1 to receive cryotherapy for 7 h (N = 46) or 2 h (N = 48). Oral mucositis was evaluated prospectively. No significant difference was observed with respect to the proportion of patients who showed grades 3 and 4 toxicity according to the WHO scale (2.1 and 4.3% for 2 and 7 h, respectively; 95% CI -0.09 to 0.049; p = 0.98) as between the groups. Two hours of cryotherapy was as effective as 7 h in terms of protecting against severe oral mucositis in connection with autologous HSCT for myeloma. This trial is registered with ClinicalTrials.gov (NCT03704597).
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http://dx.doi.org/10.1038/s41409-019-0468-6DOI Listing
September 2019

Consumption of whole grain/bran rye instead of refined wheat decrease concentrations of TNF-R2, e-selectin, and endostatin in an exploratory study in men with prostate cancer.

Clin Nutr 2020 01 15;39(1):159-165. Epub 2019 Jan 15.

Unit of Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, 171 77 Stockholm, Sweden; Department of Public Health and Clinical Medicine, Nutritional Research, Umeå University, Umeå, Sweden; Department of Biology and Biological Engineering, Division of Food and Nutrition Science, Chalmers University of Technology, Gothenburg, Sweden.

Background & Aims: Rye consumption has shown beneficial effects on prostate cancer tumors, as indicated by slower initial tumor growth in animal models and lowering of prostate-specific antigen (PSA) in humans. This study evaluated the effects of whole grain/bran rye consumption on low-grade inflammation and endothelial function biomarkers in men with prostate cancer.

Methods: Seventeen men with untreated, low-grade prostate cancer consumed 485 g rye whole grain and bran products (RP) per day or refined wheat products with added cellulose (WP) in a randomized crossover design. Fasting blood samples were taken before and after 2, 4, and 6 weeks of treatment.

Results: Concentrations of tumor nuclear factor-receptor 2 (TNF-R2), e-selectin, and endostatin were significantly lower after consumption of the RP diet compared with WP (p < 0.05). Cathepsin S concentration was positively correlated to TNF-R2 and endostatin concentrations across all occasions. Strong correlations were consistently found between intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) and between interleukin-6 (IL-6) and interleukin-1 receptor antagonist (IL-1RA). No effect of intervention was found in 92 inflammation-related protein biomarkers measured in a proximity extension assay.

Conclusions: RP diet lowered TNF-R2, e-selectin, and endostatin, compared with WP in men with prostate cancer. These effects were accompanied by a reduction in PSA.
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http://dx.doi.org/10.1016/j.clnu.2019.01.007DOI Listing
January 2020

Radical Prostatectomy or Watchful Waiting in Prostate Cancer - 29-Year Follow-up.

N Engl J Med 2018 12;379(24):2319-2329

From the Department of Surgical Sciences (A.B.-A., L.H., M.H.), Regional Cancer Center Uppsala Örebro (H.G.), and the Department of Pathology (C.B.), Uppsala University Hospital, Uppsala, the School of Health and Medical Sciences, Örebro University, and the Department of Urology, Örebro University Hospital, Örebro (S.-O.A., O.A., J.-E.J.), the Department of Medical Epidemiology and Biostatistics (H.-O.A.), Karolinska Institutet, Stockholm, and the Division of Clinical Cancer Epidemiology, Sahlgrenska Academy, Gothenburg (G.S.) - all in Sweden; the School of Medicine, Division of Cancer Studies (L.H., H.G.), and the School of Cancer and Pharmaceutical Sciences (L.H.), King's College London, London; the Department of Urology, Helsinki University Hospital (K.T.), and the Department of Pathology, University of Helsinki (S.N.), Helsinki; the Department of Epidemiology, Harvard T.C. Chan School of Public Health, Boston (H.-O.A.); and the Clinical Effectiveness Research Group, Institute of Health and Society, University of Oslo, Oslo (H.-O.A.).

Background: Radical prostatectomy reduces mortality among men with clinically detected localized prostate cancer, but evidence from randomized trials with long-term follow-up is sparse.

Methods: We randomly assigned 695 men with localized prostate cancer to watchful waiting or radical prostatectomy from October 1989 through February 1999 and collected follow-up data through 2017. Cumulative incidence and relative risks with 95% confidence intervals for death from any cause, death from prostate cancer, and metastasis were estimated in intention-to-treat and per-protocol analyses, and numbers of years of life gained were estimated. We evaluated the prognostic value of histopathological measures with a Cox proportional-hazards model.

Results: By December 31, 2017, a total of 261 of the 347 men in the radical-prostatectomy group and 292 of the 348 men in the watchful-waiting group had died; 71 deaths in the radical-prostatectomy group and 110 in the watchful-waiting group were due to prostate cancer (relative risk, 0.55; 95% confidence interval [CI], 0.41 to 0.74; P<0.001; absolute difference in risk, 11.7 percentage points; 95% CI, 5.2 to 18.2). The number needed to treat to avert one death from any cause was 8.4. At 23 years, a mean of 2.9 extra years of life were gained with radical prostatectomy. Among the men who underwent radical prostatectomy, extracapsular extension was associated with a risk of death from prostate cancer that was 5 times as high as that among men without extracapsular extension, and a Gleason score higher than 7 was associated with a risk that was 10 times as high as that with a score of 6 or lower (scores range from 2 to 10, with higher scores indicating more aggressive cancer).

Conclusions: Men with clinically detected, localized prostate cancer and a long life expectancy benefited from radical prostatectomy, with a mean of 2.9 years of life gained. A high Gleason score and the presence of extracapsular extension in the radical prostatectomy specimens were highly predictive of death from prostate cancer. (Funded by the Swedish Cancer Society and others.).
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http://dx.doi.org/10.1056/NEJMoa1807801DOI Listing
December 2018

Impact of Oral Side Effects from Conditioning Therapy Before Hematopoietic Stem Cell Transplantation: Protocol for a Multicenter Study.

JMIR Res Protoc 2018 Apr 23;7(4):e103. Epub 2018 Apr 23.

Institute of Odontology, Sahlgrenska Academy, Gothenburg, Sweden.

Background: The oral cavity is a common site of complications related to the cytotoxic effect of high-dose chemotherapy and radiation therapy. Considering our limited understanding of the burden of illness in the oral cavity from various cytotoxic therapies, it is difficult to produce evidence-based, preventive and management protocols. A prospective multicenter study is necessary to collect data on the burden of illness from various cytotoxic regimens.

Objective: The objectives of this prospective international observational multicenter study in hematopoietic stem cell transplant (HSCT) patients are to establish the nature, incidence and temporal relationship of oral complications related to conditioning regimens (chemotherapy with or without total body irradiation), stem cell transplantation and the immunologic reactions (mainly graft-vs-host-disease) that may follow, and to determine what subjective and objective oral complications related to treatment can predict negative clinical and economic outcomes and reduced quality of life.

Methods: Adult patients at six study sites receiving full intensity conditioning, reduced intensity conditioning or nonmyeloablative conditioning, followed by autologous or allogeneic hematopoietic stem cell infusion, are included. A pre-treatment assessment includes medical conditions, planned chemo- and radiation therapy regimen, medications, allergies, social history, patient report of oral problems, dental history, subjective oral complaints, objective measures of oral conditions, current laboratory values, dental treatment recommended and untreated dental disease. Starting 1-3 days after hematopoietic stem cell infusion, a bedside assessment is completed 3 days per week until resolution of neutropenia. A patient questionnaire is also completed during hospitalization. Beyond this time, patients with continued oral mucositis or other oral problems are followed 1 day per week in an inpatient or outpatient setting. Additional visits for urgent care for acute oral problems after hospitalization are documented. Autologous transplant patients are being followed up at 100 days (SD 30 days) and at 1 year (SD 30 days) post-transplantation to identify any long-term side effects. Patients treated with allogeneic transplantation are being followed at 100 days (SD 30 days), 6 months (SD 30 days), and 12 months (SD 30 days). The follow-up assessments include cancer response to therapy, current medical conditions, medications, subjective and objective oral findings, quality of life measures and laboratory values. The targeted enrollment is 254 patients who have received HSCT.

Results: A total of 260 participants have been enrolled, with 233 (91%) who have received HSCT. We anticipate enrollment of 20-30 additional participants to obtain the sample size of 254 enrolled participants who have received HSCT.

Conclusions: The results of the ongoing prospective study will provide a unique dataset to understand the impact of oral complications on patients undergoing HSCT and provide needed evidence for guidelines regarding the management of this patient cohort.
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http://dx.doi.org/10.2196/resprot.8982DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5938569PMC
April 2018

Outcome of a Salvage Third Autologous Stem Cell Transplantation in Multiple Myeloma.

Biol Blood Marrow Transplant 2018 07 3;24(7):1372-1378. Epub 2018 Feb 3.

Department of Hematology, Eppendorf University Hospital, Hamburg, Germany.

To evaluate the outcomes of salvage third autologous stem cell transplantation (ASCT) in patients with relapsed multiple myeloma. We analyzed 570 patients who had undergone a third ASCT between 1997 and 2010 (European Society for Blood and Marrow Transplantation data), of whom 482 patients underwent tandem ASCT and a third ASCT at first relapse (AARA group) and 88 patients underwent an upfront ASCT with second and third transplantations after subsequent relapses (ARARA group). With a median follow-up after salvage third ASCT of 61 months in the AARA group and 48 months in the ARARA group, the day +100 nonrelapse mortality in the 2 groups was 4% and 7%, the incidence of second primary malignancy was 6% and 7%, the median progression-free survival was 13 and 8 months, and median overall survival (OS) was 33 and 15 months. In the AARA group, according to the relapse-free interval (RFI) from the second ASCT, the median OS after the third ASCT was 17 months if the RFI was <18 months, 37 months if the RFI was between 18 and 36 months, and 64 months if the RFI was ≥36 months (P < .001). In the ARARA group, the median OS after the third ASCT was 7 months if the RFI was <6 months, 13 months if the RFI was between 6 and 18 months, and 27 months if the RFI was ≥18 months (P < .001). In a multivariate analysis of the AARA group, the favorable prognostic factor was an RFI after second ASCT of ≥18 months. Progressive disease and a Karnofsky Performance Status score of <70 at third ASCT were unfavorable factors. A salvage third ASCT is of value for patients with relapsed myeloma, particularly for those with a long duration of response and chemosensitive disease at the time of transplantation.
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http://dx.doi.org/10.1016/j.bbmt.2018.01.035DOI Listing
July 2018

Short-term side effects and attitudes towards second donation: A comparison of related and unrelated haematopoietic stem cell donors.

J Clin Apher 2018 Jun 18;33(3):226-235. Epub 2017 Aug 18.

Department of Haematology, Uppsala University Hospital, Uppsala, Sweden.

The Nordic Register of Haematopoietic Stem Cell Donors (NRHSD) has registered related and unrelated donors from 10 transplant centres in Sweden, Norway, Finland and Denmark since 1998. We present a prospective, observational study of 1,957 donors, focusing mainly on the differences between related and unrelated donors. Related donors are reported to have more comorbidities, but similar side effects compared with unrelated donors. Side effects after BM or PBSC donation are generally of short duration and in this study no deaths, myocardial infarctions, splenic ruptures, or thromboembolic events are reported. Interestingly, related donors express more hesitancy towards donating again when asked 1 month after donation.
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http://dx.doi.org/10.1002/jca.21576DOI Listing
June 2018

Allogeneic stem cell transplantation in patients with atypical chronic myeloid leukaemia: a retrospective study from the Chronic Malignancies Working Party of the European Society for Blood and Marrow Transplantation.

Br J Haematol 2017 06 28;177(5):759-765. Epub 2017 Mar 28.

University Hospital Eppendorf, Hamburg, Germany.

Atypical chronic myeloid leukaemia (aCML) is an aggressive malignancy for which allogeneic haematopoietic stem cell transplantation (allo-HSCT) represents the only curative option. We describe transplant outcomes in 42 patients reported to the European Society for Blood and Marrow Transplantation (EBMT) registry who underwent allo-HSCT for aCML between 1997 and 2006. Median age was 46 years. Median time from diagnosis to transplant was 7 months. Disease status was first chronic phase in 69%. Donors were human leucocyte antigen (HLA)-identical siblings in 64% and matched unrelated (MUD) in 36%. A reduced intensity conditioning was employed in 24% of patients. T-cell depletion was applied in 87% and 26% of transplants from MUD and HLA-identical siblings, respectively. According to the EBMT risk-score, 45% of patients were 'low-risk', 31% 'intermediate-risk' and 24% 'high-risk'. Following allo-HSCT, 87% of patients achieved complete remission. At 5 years, relapse-free survival was 36% and non-relapse mortality (NRM) was 24%, while relapse occurred in 40%. Patient age and the EBMT score had an impact on overall survival. Relapse-free survival was higher in MUD than in HLA-identical sibling HSCT, with no difference in NRM. In conclusion, this study confirmed that allo-HSCT represents a valid strategy to achieve cure in a reasonable proportion of patients with aCML, with young patients with low EBMT risk score being the best candidates.
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http://dx.doi.org/10.1111/bjh.14619DOI Listing
June 2017

Dairy intake in relation to prostate cancer survival.

Int J Cancer 2017 05 22;140(9):2060-2069. Epub 2017 Feb 22.

Department of Urology, Örebro University Hospital, Örebro, Sweden.

Dairy intake has been associated with increased risk of advanced prostate cancer. Two US cohort studies reported increased prostate cancer-specific mortality with increased high-fat milk intake. We examined whether dairy and related nutrient intake were associated with prostate cancer progression in a Swedish patient population with high dairy consumption. We prospectively followed 525 men with newly diagnosed prostate cancer (diagnosed 1989-1994). We identified and confirmed deaths through February 2011 (n = 222 prostate cancer-specific, n = 268 from other causes). Cox proportional hazards regression was used to calculate hazard ratios (HR) and 95% confidence intervals (CI) for the associations between food or nutrient intake and prostate cancer-specific death. On average, patients consumed 5.0 servings/day of total dairy products at diagnosis. In the whole population, high-fat milk intake was not associated with prostate cancer-specific death (95% CI: 0.78, 2.10; p-trend = 0.32; multivariate-adjusted model). However, among patients diagnosed with localized prostate cancer, compared to men who consumed <1 servings/day of high-fat milk, those who drank ≥3 servings/day had an increased hazard of prostate cancer mortality (HR = 6.10; 95% CI: 2.14, 17.37; p-trend = 0.004; multivariate-adjusted model). Low-fat milk intake was associated with a borderline reduction in prostate cancer death among patients with localized prostate cancer. These associations were not observed among patients diagnosed with advanced stage prostate cancer. Our data suggest a positive association between high-fat milk intake and prostate cancer progression among patients diagnosed with localized prostate cancer. Further studies are warranted to investigate this association and elucidate the mechanisms by which high-fat milk intake may promote prostate cancer progression.
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http://dx.doi.org/10.1002/ijc.30642DOI Listing
May 2017

Exposure to polychlorinated biphenyls and prostate cancer: population-based prospective cohort and experimental studies.

Carcinogenesis 2016 Dec 7;37(12):1144-1151. Epub 2016 Oct 7.

School of Health and Medical Sciences, Örebro University, Örebro SE 701 82, Sweden.

Polychlorinated biphenyls (PCBs) are highly persistent environmental pollutants and are undesirable components of our daily food. PCBs are classified as human carcinogens, but the evidence for prostate cancer is limited and available data are inconsistent. We explored the link between non-dioxin-like PCB and grade of prostate cancer in a prospective cohort as well as in cell experiments. A population-based cohort of 32496 Swedish men aged 45-79 years was followed prospectively through 1998-2011, to assess the association between validated estimates of dietary PCB exposure and incidence of prostate cancer by grade (2789 cases, whereof 1276 low grade, 756 intermediate grade, 450 high grade) and prostate cancer mortality (357 fatal cases). In addition, we investigated a non-dioxin-like PCB153-induced cell invasion and related markers in normal prostate stem cells (WPE-stem) and in three different prostate cancer cell lines (PC3, DU145 and 22RV1) at exposure levels relevant to humans. After multivariable-adjustment, dietary PCB exposure was positively associated with high-grade prostate cancer, relative risk (RR) 1.35 [95% confidence interval (CI): 1.03-1.76] and with fatal prostate cancer, RR 1.43 (95% CI: 1.05-1.95), comparing the highest tertile with the lowest. We observed no association with low or intermediate grade of prostate cancer. Cell invasion and related markers, including MMP9, MMP2, Slug and Snail, were significantly increased in human prostate cancer cells as well as in prostate stem cells after exposure to PCB153. Our findings both from the observational and experimental studies suggest a role of non-dioxin-like PCB153 in the development of high-grade and fatal prostate cancer.
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http://dx.doi.org/10.1093/carcin/bgw105DOI Listing
December 2016

Colonoscopy and Sigmoidoscopy are Equally Effective for the Diagnosis of Colonic Acute Graft-versus-Host Disease in Patients with Diarrhea after Allogeneic Stem Cell Transplantation: A Prospective Controlled Trial.

Biol Blood Marrow Transplant 2015 Dec 14;21(12):2086-2090. Epub 2015 Jul 14.

Department of Gastroenterology, Sahlgrenska University Hospital, Göteborg, Sweden.

Colonic acute graft-versus-host disease (aGVHD) affects approximately 10% of patients who have undergone allogeneic stem cell transplantation (allo-SCT). Diarrhea is a major clinical sign but also a common post-transplantation symptom in these patients. Comprehensive histopathologic examination of the colon is therefore regarded as crucial to establish a diagnosis, but the colonic segment that should be targeted for a diagnostic biopsy remains a topic of debate. The primary objective of this study was to compare prospectively colonoscopy with sigmoidoscopy regarding their capabilities to provide a histopathologically proven diagnosis of colonic aGVHD. Thirty-seven allo-SCT patients with diarrhea all underwent a colonoscopy. All biopsies collected from the descending colon were regarded as also attainable by sigmoidoscopy, whereas biopsies collected in regions further up the colon (from the transverse and ascending colon) were regarded as acquirable exclusively by colonoscopy. Biopsies attainable by colonoscopy and sigmoidoscopy were positive for GVHD in 25 (68%) and 24 (65%) patients, respectively (95% confidence interval for difference of proportions, -.185 to .245; P = .978; z = .0271 by the z-test). Sigmoidoscopy is as effective as colonoscopy in establishing a diagnosis of colonic aGVHD in patients who have diarrhea after allo-SCT.
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http://dx.doi.org/10.1016/j.bbmt.2015.07.009DOI Listing
December 2015

Measuring PI3K Activation: Clinicopathologic, Immunohistochemical, and RNA Expression Analysis in Prostate Cancer.

Mol Cancer Res 2015 Oct 29;13(10):1431-40. Epub 2015 Jun 29.

Center for Molecular Oncologic Pathology, Dana-Farber Cancer Institute, Boston, Massachusetts. Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts. Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts. Broad Institute of Harvard and MIT, Cambridge, Massachusetts. Division of Cancer Studies, King's College London, London, United Kingdom.

Unlabelled: Assessing the extent of PI3K pathway activity in cancer is vital to predicting sensitivity to PI3K-targeting drugs, but the best biomarker of PI3K pathway activity in archival tumor specimens is unclear. Here, PI3K pathway activation was assessed, in clinical tissue from 1,021 men with prostate cancers, using multiple pathway nodes that include PTEN, phosphorylated AKT (pAKT), phosphorylated ribosomal protein S6 (pS6), and stathmin. Based on these markers, a 9-point score of PI3K activation was created using the combined intensity of the 4-markers and analyzed its association with proliferation (Ki67), apoptosis (TUNEL), and androgen receptor (AR) status, as well as pathologic features and cancer-specific outcomes. In addition, the PI3K activation score was compared with mRNA expression profiling data for a large subset of men. Interestingly, those tumors with higher PI3K activation scores also had higher Gleason grade (P = 0.006), increased AR (r = 0.37; P < 0.001) and Ki67 (r = 0.24; P < 0.001), and decreased TUNEL (r = -0.12; P = 0.003). Although the PI3K activation score was not associated with an increased risk of lethal outcome, a significant interaction between lethal outcome, Gleason and high PI3K score (P = 0.03) was observed. Finally, enrichment of PI3K-specific pathways was found in the mRNA expression patterns differentiating the low and high PI3K activation scores; thus, the 4-marker IHC score of PI3K pathway activity correlates with features of PI3K activation.

Implications: The relationship of this activation score to sensitivity to anti-PI3K agents remains to be tested but may provide more precision guidance when selecting patients for these therapies.
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http://dx.doi.org/10.1158/1541-7786.MCR-14-0569DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4618038PMC
October 2015

Survival benefit of early androgen receptor inhibitor therapy in locally advanced prostate cancer: long-term follow-up of the SPCG-6 study.

Eur J Cancer 2015 Jul 16;51(10):1283-92. Epub 2015 Apr 16.

Copenhagen Prostate Cancer Center, Department of Urology, Rigshospitalet, University of Copenhagen, Denmark.

Background: The optimal timing of endocrine therapy in non-metastatic prostate cancer (PCa) is still an issue of debate.

Methods: A randomised, double-blind, parallel-group trial comparing bicalutamide 150mg once daily with placebo in addition to standard care in patients with hormone-naïve, non-metastatic PCa. Kaplan-Meier analysis was used to estimate overall survival (OS) and multivariate Cox proportional hazard model was performed to analyse time-to-event (death).

Findings: A total of 1218 patients were included into the Scandinavian Prostate Cancer Group (SPCG)-6 study of which 607 were randomised to receive bicalutamide in addition to their standard care and 611 to receive placebo. Median follow-up was 14.6years. Overall, 866 (71.1%) patients died, 428 (70.5%) in the bicalutamide arm and 438 (71.7%) in the placebo arm, p=0.87. Bicalutamide significantly improved OS in patient with locally advanced disease (hazard ratios (HR)=0.77 (95% confidence interval (CI): 0.63-0.94, p=0.01), regardless of baseline prostate-specific antigen (PSA), with a survival benefit which was apparent throughout the study period. In contrast, survival favoured randomisation to the placebo arm in patients with localised disease (HR=1.19 (95% CI: 1.00-1.43), p=0.056). However, a survival gain from bicalutamide therapy was present in patients with localised disease and a baseline PSA greater than 28ng/mL at randomisation. In multivariate Cox proportional hazard model, only including patients managed on watchful waiting as their standard of care (n=991) OS depended on age, World Health Organisation (WHO) grade, baseline PSA, clinical stage and randomised treatment.

Interpretation: Throughout the 14.6year follow-up period the addition of early bicalutamide to standard of care resulted in a significant OS benefit in patients with locally advanced PCa. In contrast, patients with localised PCa and low PSA derived no survival benefit from early bicalutamide. The optimal timing for initiating bicalutamide in non-metastatic PCa patients is dependent on disease stage and baseline PSA.
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http://dx.doi.org/10.1016/j.ejca.2015.03.021DOI Listing
July 2015

Eosinophils in the blood of hematopoietic stem cell transplanted patients are activated and have different molecular marker profiles in acute and chronic graft-versus-host disease.

Immun Inflamm Dis 2014 Aug 7;2(2):99-113. Epub 2014 Jul 7.

Department of Infectious Diseases, Sahlgrenska Academy, University of Gothenburg Göteborg, Sweden.

While increased numbers of eosinophils may be detected in patients with graft-versus-host disease (GVHD) following hematopoietic stem cell transplantation, it is not known if eosinophils play a role in GVHD. The aims of this study were to determine: whether eosinophils are activated during GVHD; whether the patterns of activation are similar in acute and chronic GVHD; and the ways in which systemic corticosteroids affect eosinophils. Transplanted patients (n = 35) were investigated for eosinophil numbers and the expression levels of 16 eosinophilic cell surface markers using flow cytometry; all the eosinophil data were analyzed by the multivariate method OPLS-DA. Different patterns of molecule expression were observed on the eosinophils from patients with acute, chronic, and no GVHD, respectively. The molecules that provided the best discrimination between acute and chronic GVHD were: the activation marker CD9; adhesion molecules CD11c and CD18; chemokine receptor CCR3; and prostaglandin receptor CRTH2. Patients with acute or chronic GVHD who received systemic corticosteroid treatment showed down-regulation of the cell surface markers on their eosinophils, whereas corticosteroid treatment had no effect on the eosinophil phenotype in the patients without GVHD. In summary, eosinophils are activated in GVHD, display different activation profiles in acute and chronic GVHD, and are highly responsive to systemic corticosteroids.
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http://dx.doi.org/10.1002/iid3.25DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4217552PMC
August 2014

Eosinophils from hematopoietic stem cell recipients suppress allogeneic T cell proliferation.

Biol Blood Marrow Transplant 2014 Dec 28;20(12):1891-8. Epub 2014 Aug 28.

Department of Infectious Diseases, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.

Eosinophilia has been associated with less severe graft-versus-host disease (GVHD), but the underlying mechanism is unknown. We hypothesized that eosinophils diminish allogeneic T cell activation in patients with chronic GVHD. The capacity of eosinophils derived from healthy subjects and hematopoietic stem cell (HSC) transplant recipients, with or without chronic GVHD, to reduce allogeneic T cell proliferation was evaluated using a mixed leukocyte reaction. Eosinophil-mediated inhibition of proliferation was observed for the eosinophils of both healthy subjects and patients who underwent HSC transplantation. Eosinophils from patients with and without chronic GVHD were equally suppressive. Healthy eosinophils required cell-to-cell contact for their suppressive capacity, which was directed against CD4(+) T cells and CD8(+) T cells. Neither eosinophilic cationic protein, eosinophil-derived neurotoxin, indoleamine 2,3-dioxygenase, or increased numbers of regulatory T cells could account for the suppressive effect of healthy eosinophils. Real-time quantitative PCR analysis revealed significantly increased mRNA levels of the immunoregulatory protein galectin-10 in the eosinophils of both chronic GVHD patients and patients without GVHD, as compared with those from healthy subjects. The upregulation of galectin-10 expression in eosinophils from patients suggests a stimulatory effect of HSC transplantation in itself on eosinophilic galectin-10 expression, regardless of chronic GVHD status. To conclude, eosinophils from HSC transplant recipients and healthy subjects have a T cell suppressive capacity.
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http://dx.doi.org/10.1016/j.bbmt.2014.08.017DOI Listing
December 2014

Radical prostatectomy or watchful waiting in early prostate cancer.

N Engl J Med 2014 Mar;370(10):932-42

From the Departments of Surgical Sciences (A.B.-A., M.H.) and Immunology, Genetics, and Pathology (C.B.), and the Regional Cancer Center Uppsala Örebro (L.H., H.G.), Uppsala University Hospital, Uppsala, the School of Health and Medical Sciences, Örebro University and Department of Urology, Örebro University Hospital, Örebro (S.-O.A., O.A., J.-E.J.), the Department of Urology, Linköping University Hospital, Linköping (A.S.), the Department of Oncology and Pathology, Division of Clinical Cancer Epidemiology (G.S.), and Department of Medical Epidemiology and Biostatistics (J.P., H.-O.A.), Karolinska Institutet, Stockholm, and the Division of Clinical Cancer Epidemiology, Sahlgrenska Academy, Gothenburg (G.S.) - all in Sweden; King's College London, School of Medicine, Division of Cancer Studies, London (L.H., H.G.); Channing Laboratory, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School (J.R.R.), and the Department of Epidemiology, Harvard School of Public Health (J.R.R., H.-O.A.) - all in Boston; and the Department of Urology, Helsinki University Central Hospital (K.T.), and the Department of Pathology, University of Helsinki (S.N.) - both in Helsinki.

Background: Radical prostatectomy reduces mortality among men with localized prostate cancer; however, important questions regarding long-term benefit remain.

Methods: Between 1989 and 1999, we randomly assigned 695 men with early prostate cancer to watchful waiting or radical prostatectomy and followed them through the end of 2012. The primary end points in the Scandinavian Prostate Cancer Group Study Number 4 (SPCG-4) were death from any cause, death from prostate cancer, and the risk of metastases. Secondary end points included the initiation of androgen-deprivation therapy.

Results: During 23.2 years of follow-up, 200 of 347 men in the surgery group and 247 of the 348 men in the watchful-waiting group died. Of the deaths, 63 in the surgery group and 99 in the watchful-waiting group were due to prostate cancer; the relative risk was 0.56 (95% confidence interval [CI], 0.41 to 0.77; P=0.001), and the absolute difference was 11.0 percentage points (95% CI, 4.5 to 17.5). The number needed to treat to prevent one death was 8. One man died after surgery in the radical-prostatectomy group. Androgen-deprivation therapy was used in fewer patients who underwent prostatectomy (a difference of 25.0 percentage points; 95% CI, 17.7 to 32.3). The benefit of surgery with respect to death from prostate cancer was largest in men younger than 65 years of age (relative risk, 0.45) and in those with intermediate-risk prostate cancer (relative risk, 0.38). However, radical prostatectomy was associated with a reduced risk of metastases among older men (relative risk, 0.68; P=0.04).

Conclusions: Extended follow-up confirmed a substantial reduction in mortality after radical prostatectomy; the number needed to treat to prevent one death continued to decrease when the treatment was modified according to age at diagnosis and tumor risk. A large proportion of long-term survivors in the watchful-waiting group have not required any palliative treatment. (Funded by the Swedish Cancer Society and others.).
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http://dx.doi.org/10.1056/NEJMoa1311593DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4118145PMC
March 2014

Autologous haematopoietic stem cell transplantation for aggressive multiple sclerosis: the Swedish experience.

J Neurol Neurosurg Psychiatry 2014 Oct 19;85(10):1116-21. Epub 2014 Feb 19.

Department of Neuroscience, Uppsala University, Uppsala, Sweden Department of Neurology, Uppsala University Hospital, Uppsala, Sweden.

Background: Autologous haematopoietic stem cell transplantation (HSCT) is a viable option for treatment of aggressive multiple sclerosis (MS). No randomised controlled trial has been performed, and thus, experiences from systematic and sustained follow-up of treated patients constitute important information about safety and efficacy. In this observational study, we describe the characteristics and outcome of the Swedish patients treated with HSCT for MS.

Methods: Neurologists from the major hospitals in Sweden filled out a follow-up form with prospectively collected data. Fifty-two patients were identified in total; 48 were included in the study and evaluated for safety and side effects; 41 patients had at least 1 year of follow-up and were further analysed for clinical and radiological outcome. In this cohort, 34 patients (83%) had relapsing-remitting MS, and mean follow-up time was 47 months.

Results: At 5 years, relapse-free survival was 87%; MRI event-free survival 85%; expanded disability status scale (EDSS) score progression-free survival 77%; and disease-free survival (no relapses, no new MRI lesions and no EDSS progression) 68%. Presence of gadolinium-enhancing lesions prior to HSCT was associated with a favourable outcome (disease-free survival 79% vs 46%, p=0.028). There was no mortality. The most common long-term side effects were herpes zoster reactivation (15%) and thyroid disease (8.4%).

Conclusions: HSCT is a very effective treatment of inflammatory active MS and can be performed with a high degree of safety at experienced centres.
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http://dx.doi.org/10.1136/jnnp-2013-307207DOI Listing
October 2014

High incidence of chronic graft-versus-host disease after myeloablative allogeneic stem cell transplantation for chronic lymphocytic leukemia in Sweden: graft-versus-leukemia effect protects against relapse.

Med Oncol 2013 Dec 9;30(4):762. Epub 2013 Nov 9.

Division of Hematology, Department of Medicine at Huddinge, Karolinska Institutet, Stockholm, Sweden,

Allogeneic hematopoietic stem cell transplantation (allo-SCT) is a potentially curative treatment option for eligible patients with chronic lymphocytic leukemia (CLL). However, it is known that cure of CLL is only possible if a graft-versus-leukemia effect is present. Between 1994 and 2007, 48 adults underwent allo-SCT for poor-risk CLL in Sweden. Of these, ten (21%) patients aged 24-53 years (median: 46 years) received myeloablative conditioning (MAC), based on TBI and cyclophosphamide. All MAC patients had refractory, poorly controlled CLL before allo-SCT (partial remission in 9/10 patients and progressive disease in one). The cumulative incidence of acute graft-versus-host disease (GVHD) grades II-IV was 30%. Nine patients developed chronic GVHD; extensive in four. Rates of nonrelapse mortality at 1, 3 and 10 years were 0, 10 and 20%, respectively. Two patients relapsed 36 and 53 months after transplantation. Six patients were still alive after a median follow-up time of 11.5 years (range 5.9-13.7). The probabilities of relapse-free and overall survival from 1, 3 and 5 years after transplantation were 100, 90 and 70%, and 100, 90 and 80%, respectively. Nevertheless, our analysis of long-term outcome after MAC allo-SCT for CLL suggests that younger patients with poorly controlled CLL may benefit from MAC allo-SCT.
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http://dx.doi.org/10.1007/s12032-013-0762-xDOI Listing
December 2013

Lifetime body size and prostate cancer risk in a population-based case-control study in Sweden.

Cancer Causes Control 2013 Dec 19;24(12):2143-55. Epub 2013 Sep 19.

Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, P.O. Box 281, SE-171 77, Stockholm, Sweden,

Purpose: The role of body size in prostate cancer etiology is unclear and potentially varies by age and disease subtype. We investigated whether body size in childhood and adulthood, including adult weight change, is related to total, low-intermediate-risk, high-risk, and fatal prostate cancer.

Methods: We used data on 1,499 incident prostate cancer cases and 1,118 population controls in Sweden. Body figure at age 10 was assessed by silhouette drawings. Adult body mass index (BMI) and weight change were based on self-reported height and weight between ages 20 and 70. We estimated odds ratios (ORs) with 95 % confidence intervals (CIs) by unconditional logistic regression.

Results: Height was positively associated with prostate cancer. Overweight/obesity in childhood was associated with a 54 % increased risk of dying from prostate cancer compared to normal weight, whereas a 27 % lower risk was seen in men who were moderately thin (drawing 2) in childhood (P trend = 0.01). Using BMI <22.5 as a reference, we observed inverse associations between BMI 22.5 to <25 at age 20 and all prostate cancer subtypes (ORs in the range 0.72-0.82), and between mean adult BMI 25 to <27.5 and low-intermediate-risk disease (OR 0.75, 95 % CI 0.55-1.02). Moderate adult weight gain increased the risk of disease in men with low BMI at start and in short men.

Conclusions: Our comprehensive life-course approach revealed no convincing associations between anthropometric measures and prostate cancer risk. However, we found some leads that deserve further investigation, particularly for early-life body size. Our study highlights the importance of the time window of exposure in prostate cancer development.
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http://dx.doi.org/10.1007/s10552-013-0291-0DOI Listing
December 2013

Intermittent versus indwelling urinary catheterisation in hip surgery patients: a randomised controlled trial with cost-effectiveness analysis.

Int J Nurs Stud 2013 Dec 12;50(12):1589-98. Epub 2013 Jun 12.

Department of Orthopaedics, Örebro University Hospital, Örebro, Sweden; School of Health and Medical Sciences, Örebro University, Örebro, Sweden. Electronic address:

Background: Hip surgery is associated with the risk of postoperative urinary retention. To avoid urinary retention hip surgery patients undergo urinary catheterisation. Urinary catheterisation, however, is associated with increased risk for urinary tract infection (UTI). At present, there is limited evidence for whether intermittent or indwelling urinary catheterisation is the preferred choice for short-term bladder drainage in patients undergoing hip surgery.

Objectives: The aim of the study was to investigate differences between intermittent and indwelling urinary catheterisation in hip surgery patients in relation to nosocomial UTI and cost-effectiveness.

Design: Randomised controlled trial with cost-effectiveness analysis.

Setting: The study was carried out at an orthopaedic department at a Swedish University Hospital.

Methods: One hundred and seventy hip surgery patients (patients with fractures or with osteoarthritis) were randomly allocated to either intermittent or indwelling urinary catheterisation. Data collection took place at four time points: during stay in hospital, at discharge and at 4 weeks and 4 months after discharge.

Results: Eighteen patients contracted nosocomial UTIs, 8 in the intermittent catheterisation group and 10 in the indwelling catheterisation group (absolute difference 2.4%, 95% CI -6.9-11.6%) The patients in the intermittent catheterisation group were more often catheterised (p<0.001) and required more bladder scans (p<0.001) but regained normal bladder function sooner than the patients in the indwelling catheterisation group (p<0.001). Fourteen percent of the patients in the intermittent group did not need any catheterisation. Cost-effectiveness was similar between the indwelling and intermittent urinary catheterisation methods.

Conclusions: Both indwelling and intermittent methods could be appropriate in clinical practice. Both methods have advantages and disadvantages but by not using routine indwelling catheterisation, unnecessary catheterisations might be avoided in this patient group.
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http://dx.doi.org/10.1016/j.ijnurstu.2013.05.007DOI Listing
December 2013

Long-term distress after radical prostatectomy versus watchful waiting in prostate cancer: a longitudinal study from the Scandinavian Prostate Cancer Group-4 randomized clinical trial.

Eur Urol 2013 Dec 26;64(6):920-8. Epub 2013 Feb 26.

Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.

Background: Studies enumerating the dynamics of physical and emotional symptoms following prostate cancer (PCa) treatment are needed to guide therapeutic strategy. Yet, overcoming patient selection forces is a formidable challenge for observational studies comparing treatment groups.

Objective: To compare patterns of symptom burden and distress in men with localized PCa randomized to radical prostatectomy (RP) or watchful waiting (WW) and followed up longitudinally.

Design, Setting, And Participants: The three largest, Swedish, randomization centers for the Scandinavian Prostate Cancer Group-4 trial conducted a longitudinal study to assess symptoms and distress from several psychological and physical domains by mailed questionnaire every 6 mo for 2 yr and then yearly through 8 yr of follow-up.

Intervention: RP compared with WW.

Outcome Measurements And Statistical Analysis: A questionnaire was mailed at baseline and then repeatedly during follow-up with questions concerning physical and mental symptoms. Each analysis of quality of life was based on a dichotomization of the outcome (yes vs no) studied in a binomial response, generalized linear mixed model.

Results And Limitations: Of 347 randomized men, 272 completed at least five questionnaires during an 8-yr follow-up period. Almost all men reported that PCa negatively influenced daily activities and relationships. Health-related distress, worry, feeling low, and insomnia were consistently reported by approximately 30-40% in both groups. Men in the RP group consistently reported more leakage, impaired erection and libido, and fewer obstructive voiding symptoms. For men in the WW group, distress related to erectile symptoms increased gradually over time. Symptom burden and distress at baseline was predictive of long-term outlook.

Conclusions: Cancer negatively influenced daily activities among almost all men in both treatment groups; health-related distress was common. Trade-offs exist between physiologic symptoms, highlighting the importance of tailored treatment decision-making. Men who are likely to experience profound long-term distress can be identified early in disease management.
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http://dx.doi.org/10.1016/j.eururo.2013.02.025DOI Listing
December 2013

Results from the Scandinavian Prostate Cancer Group Trial Number 4: a randomized controlled trial of radical prostatectomy versus watchful waiting.

J Natl Cancer Inst Monogr 2012 Dec;2012(45):230-3

Division of Cancer Studies, Guy's Hospital, King's College London, St Thomas Street, London, UK.

In the Scandinavian Prostate Cancer Group Trial Number 4 (SPCG-4), 347 men were randomly assigned to radical prostatectomy and 348 to watchful waiting. In the most recent analysis (median follow-up time = 12.8 years), the cumulative mortality curves had been stable over the follow-up. At 15 years, the absolute risk reduction of dying from prostate cancer was 6.1% following randomization to radical prostatectomy, compared with watchful waiting. Hence, 17 need to be randomized to operation to avert one death. Data on self-reported symptoms, stress from symptoms, and quality of life were collected at 4 and 12.2 years of median follow-up. These questionnaire studies show an intricate pattern of symptoms evolving after surgery, hormonal treatments, signs of tumor progression, and also from natural aging. This article discusses some of the main findings of the SPCG-4 study.
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http://dx.doi.org/10.1093/jncimonographs/lgs025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3540876PMC
December 2012

Natural history of early, localized prostate cancer: a final report from three decades of follow-up.

Eur Urol 2013 Mar 13;63(3):428-35. Epub 2012 Oct 13.

School of Health and Medical Sciences, Örebro University; and Department of Urology, Örebro University Hospital, Örebro, Sweden.

Background: Most localized prostate cancers are believed to have an indolent course. Within 15 yr of diagnosis, most deaths among men with prostate cancer (PCa) can be attributed to other competing causes. However, data from studies with extended follow-up are insufficient to determine appropriate treatment for men with localized disease.

Objective: To investigate the long-term natural history of untreated, early-stage PCa.

Design, Setting, And Participants: We conducted a population-based, prospective-cohort study using a consecutive sample of 223 patients with untreated, localized PCa from a regionally well-defined catchment area in central Sweden. All subjects were initially managed with observation. Androgen deprivation therapy was administered when symptomatic tumor progression occurred.

Outcome Measurements And Statistical Analysis: Based on >30 yr of follow-up, the main outcome measures were: progression-free, cause-specific, and overall survival, and rates of progression and mortality per 1000 person-years.

Results And Limitations: After 32 yr of follow-up, all but 3 (1%) of the 223 men had died. We observed 90 (41.4%) local progression events and 41 (18.4%) cases of progression to distant metastasis. In total, 38 (17%) men died of PCa. Cause-specific survival decreased between 15 and 20 yr, but stabilized with further follow-up. All nine men with Gleason grade 8-10 disease died within the first 10 yr of follow-up, five (55%) from PCa. Survival for men with well-differentiated, nonpalpable tumors declined slowly through 20 yr, and more rapidly between 20 and 25 yr (from 75.2% [95% confidence interval, 48.4-89.3] to 25% [95% confidence interval, 22.0-72.5]). It is unclear whether these data are relevant for tumors detected by elevated prostate-specific antigen levels.

Conclusions: Although localized PCa most often has an indolent course, local progression and distant metastasis can develop over the long term, even among patients considered low risk at diagnosis.
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http://dx.doi.org/10.1016/j.eururo.2012.10.002DOI Listing
March 2013

Initial symptoms and delay in patients with penile carcinoma.

Scand J Urol Nephrol 2012 Oct 2;46(5):319-25. Epub 2012 Jul 2.

Department of Urology, Örebro University Hospital, Örebro, Sweden.

Objective: This study aimed to assess initial symptoms and factors associated with patients' and doctors' delay in penile carcinoma.

Material And Methods: Fifty consecutive patients with penile carcinoma treated with an organ-sparing technique and nine with partial amputation were enrolled in a prospective study at the Department of Urology, Örebro University Hospital, between 2005 and 2009. Face-to-face structured interviews in combination with self-assessment forms were used for the patients' descriptions of clinical symptoms, treatment seeking and reasons for delay. Data were also extracted from the medical records confirming time-lag between GP assessment, specialist care and time for diagnosis.

Results: Erythema, rash and eczema were the most common initial symptoms (35%). In total, 65% had a patients' delay of more than 6 months, and among these there was a small, but not statistically significant, predominance for pT1 and pTis tumours. Living with a stable partner did not affect the delay. The most common reason for patients' delay was the feeling of embarrassment over symptoms localized in a sexual body area. Nine patients had a doctors' delay of more than 3 months from first special visit to diagnosis. Eight of these patients consulted dermatologists and were subjected to repeated biopsies, leaving premalignant results.

Conclusions: A considerable proportion of the patients had a patients' delay of more than 6 months, perhaps due to benign initial symptoms as erythema, rash or eczema. Psychological factors such as embarrassment and denial may also be involved, as well as insufficient awareness or knowledge.
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http://dx.doi.org/10.3109/00365599.2012.677473DOI Listing
October 2012