| 1. |
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| 2. |
- Venetsanos, Dimitrios
(författare)
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Improving management of STEMI patients treated with primary PCI : Pharmacotherapy, renal function estimation and gender perspective
- 2017
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis focused on the acute management of patients with ST-segment elevation myocardial infarction (STEMI) in an effort to provide information that may improve outcome. The aim was to evaluate the efficacy and safety of bivalirudin versus unfractionated heparin (UFH) in STEMI patients during primary PCI. Furthermore, to provide pharmacodynamic data of novel ways of ticagrelor administration compared to standard tivcagrelor. Additionally, to identify subgroups of patients, such as women who may derive greater benefit from specific antithrombotic strategies due to their risk/benefit profile. Finally, to evaluate current formulas for estimation of renal function in the acute phase of STEMI.In Paper I, all STEMI patients in Sweden between 2008 and 2014, treated with primary PCI and UFH or bivalirudin were included in our analysis. Of the total population of 23 800 patients, 8 783 (36.9%) were included in the UFH group and 15 017 (63.1%) in the bivalirudin group. Concomitant GPI administration was 68.5% in the UFH arm compared to 3.5% in the bivalirudin arm (p<0.01).The adjusted incidence of 30-day mortality was not significant different between the two groups (UFH vs bivalirudin, adjusted HR 0.94; 95% CI 0.82 -1.07). The adjusted risk for 1-year mortality, 30-day and 1-year stent thrombosis and re-infarction did not differ significantly between the two groups. In contrast, patients treated with UFH had a significantly higher incidence of major in-hospital bleeding (adjusted OR 1.62; 95%CI 1.30 -2.03).In Paper II pharmacodynamic data of chewed or crushed ticagrelor compared to standard ticagrelor loading dose (LD) was assessed in 99 patients with stable angina. Platelet reactivity (PR) was assessed with VerifyNow before, 20 and 60 minutes after LD. High Residual platelet reactivity (HRPR) was defined as > 208 P2Y12 reaction units (PRU). Chewed ticagrelor tablets resulted in significantly lower PRU values compared to crushed or integral tablets at 20 and 60 minutes. Crushed ticagrelor LD resulted in significantly lower PRU values compared to integral tablets at 20 minutes whereas no difference was observed at 60 minutes. At 20 minutes, no patients had HRPR with chewed ticagrelor compared to 68% with integral and 30% with crushed ticagrelor LD (p<0.01).In Paper III we presented a pre-specified gender analysis of the ATLANTIC trial including 1 862 STEMI patients that were randomly assigned to pre-hospital versus in-hospital administration of 180mg ticagrelor. Women were older and had higher TIMI risk score. Women had a 3-fold higher risk for all-cause mortality compared to men (5.7% vs 1.9%, HR 3.13, 95% CI 1.78 – 5.51). However, after adjustment for baseline characteristics, the difference was lesser and no longer significant (HR 1.98, 95% CI 0.97 – 4.04). Female gender was not an independent predictor of risk for bleeding after multivariable adjustments (BARC type 3-5 HR 1.52, 95% CI 0.74-3.09). There was no interaction between gender and efficacy or safety of randomised treatment.In Paper IV, forty patients with PCI- treated STEMI were included between November 2011 and February 2013. We validated the performance of the Cockcroft-Gault (CG), the Modification of Diet in Renal Disease (MDRD-IDMS), the Chronic Kidney Disease Epidemiology (CKD-EPI) and the Grubb relative cystatin C (rGCystC) equations for estimation of GFR against measured GFR (mGFR) during the index hospitalisation for STEMI.MDRD-IDMS and CKD-EPI demonstrated a good performance to estimate GFR with accuracy within 30% (P30) 82.5% vs 82.5%, respectively. CKD was best classified by CKD-EPI (Kappa 0.83). CG showed the worst performance with the lowest P30. The rG-CystC equation had a marked bias of -17.8% and significantly underestimated mGFR (p=0.03).Conclusions – In STEMI patients treated with primary PCI, bivalirudin should be preferred in patient at high risk for bleeding. With crushed or chewed ticagrelor tablets a more rapid platelet inhibition may be achieved, compared with standard integral tablets. In STEMI patients, fast and potent platelet inhibition with chewed ticagrelor may reduce the risk of early stent thrombosis and patients treated with a less aggressive antithrombotic strategy, such as UFH or bivalirudin monotherapy, may derive a greater benefit. Although gender differences in adverse outcomes could mainly be explained by older age and clustering of comorbidities in women, a bleedreduction strategy in women with high risk characteristics is warranted in order to improve their outcome. Regardless the choice of antithrombotic strategy, dose adjustment of drugs cleared by kidneys based on GFR estimation is of crucial importance. MDRD and CKD-EPI should be the formulas used for estimation of GFR in STEMI patients
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| 3. |
- Klaff, Rami, 1971-
(författare)
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Disease-Specific Survival in Prostate Cancer Patients : Results from the Scandinavian Prostate Cancer Group (SPCG) Trial No. 5 and Regional Cancer Register Data
- 2016
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- IntroductionProstate cancer (PCa) is the most common cancer among men in Sweden. The clinical course varies considerably, which makes it difficult to predict the prognosis in the individual case. In order to explore the early as well as the late course of the disease, large study groups and population-based cohorts are necessary.AimsTo explore factors that influence the long-term outcome of men with low-risk tumours in a population-based register, to predict the long-term course, and to assess the mortality rate for men with prostate cancer (Paper I)To analyse long-term outcome and to investigate factors associated with long-term survival in patients with metastases to the skeleton (Paper II)To analyse early androgen deprivation treatment (ADT) failure and to define clinical predictors associated with short survival due to early ADT failure in prostate cancer patients with bone metastases (Paper III)To analyse the prognostic significance of the extent of bone metastases in relation to other pretreatment variables in prostate cancer patients, and to explore the impact of bone metastases on quality-of-life (Paper IV)Material and methodsThe study groups were assembled from The South East Region Prostate Cancer Register (SERPCR), and The Scandinavian Prostate Cancer Group (SPCG) Trial No. 5. In the first study, prognostic factors and long-term disease-specific mortality rates of low-risk prostate cancer patients from the early PSA era were analysed. In the second study, patient-related factors, quality-of-life (QoL) and long-term survival in 915 PCa patients with bone metastases (M1b) under ADT, were analysed. In Study III factors predicting primary failure to respond to ADT were identified. Study IV explored the impact of the extent of bone metastases on survival and QoL for these men.Result and conclusionsThe long-term disease-specific mortality of low-risk localised PCa is low, but the annual mortality rate gradually increases. This indicates that some tumours slowly develop into lethal cancer, particularly in men 70 years or older and with a PSA level ≥ 4 μg/L. From the SPCG Trial No. 5, a subgroup of patients with M1b disease and favourable set of predictive factors survived more than 10 years under ADT with an acceptable QoL. Independent predictors of long-term survival were identified as performance status (PS) < 2, limited extent of bone metastases, and a PSA level < 231 μg/L at the time of enrolment in the trial. However, four independent clinical predictors of early ADT failure could be defined. Men exhibiting these features should be considered for an alternative treatment. Patient grouping based on three categories of extent of bone metastases related to PS, haemoglobin, and QoL at presentation, as independent predictors of mortality, may provide improved accuracy of prognosis.
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| 4. |
- Slind Olsen, Renate
(författare)
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Circulating and genetic factors in colorectal cancer : Potential factors for establishing prognosis?
- 2017
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Colorectal cancer (CRC) is defined as a cancer appearing in the colon or in the rectum. In Sweden, ~ 6300 individuals were diagnosed with the disease in 2014 and ~ 2550 individuals diagnosed with CRC die each year due to their cancer. Surgery is the main treatment option of CRC and a survival rate of ~ 10 % is estimated if distant metastases have developed. It is therefore of importance to find factors that may be useful together with tumour, node, metastasis (TNM) stage to establish early CRC diagnosis, prognosis and follow-up of CRC patients. The aim of this thesis was to study the possible association of CD93, PLA2G4C, PDGF-D and inflammatory cytokines with CRC disease progression.In a prospective study approach CD93 and PLA2G4C single nucleotide polymorphisms (SNPs) were of potential importance in CRC prognosis.The T/T genotype of CD93 was associated with an increased CD93 expression in CRC tissue. Further, CRC patients carrying this genotype were associated with disseminated CRC at diagnosis and a lower recurrence-free survival after surgery. The A allele of a SNP of PLA2G4C was a stronger predictor for CRC-specific mortality than the conventional risk factors used in the clinic for selection of TNM stage II patients for adjuvant treatment. This indicates that the T/T genotype of CD93 and the A allele of PLA2G4C may be potential genetic factors related to disease severity and spread. Furthermore, they distinguish CRC patients that may benefit from a more comprehensive follow-up and adjuvant treatment.To study the putative involvement of PDGF-D in CRC the effects of PDGF-D signalling was studied in vitro. PDGF-D signalling altered the expression of genes of importance in CRC carcinogenesis and proliferation which was blocked by imatinib, a tyrosine kinase inhibitor. This indicates that PDGF-D signalling may be an important pathway in CRC progression and a potential target in CRC treatment.The analysis of various inflammatory cytokines in plasma at diagnosis showed an association between high levels and increased total- or CRC-specific mortality two years after surgery. High levels of CCL1 and CCL24 was the only cytokines strongly correlated with a worse CRC prognosis after statistical adjustments and may be of interest for further evaluation.In conclusion, this thesis presents circulating and genetic factors such as CD93, PLA2G4C, PDGF-D, CCL1 and CCL24 that may be of importance in CRC progression and may be of clinical value together with TNM stage in establishing prognosis.
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| 5. |
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| 6. |
- Aljabery, Firas
(författare)
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Staging and tumor biological mechanisms of lymph node metastasis in invasive urinary bladder cancer
- 2017
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Aim: To study the possibility of detecting lymph node metastasis in locally advanced urinary bladder cancer (UBC) treated with radical cystectomy (RC) by using preoperative positron emission tomography/computed tomography (PET/CT) and peroperative sentinel node biopsy (SNB) technique. We also investigate the clinical significance of macrophage traits expression by cancer cells, M2-macrophage infiltration (MI) in tumor stroma and the immunohistochemical expression of biomarkers in cancer cells in relation to clinicopathologic data.Patients and Methods: We studied prospectively 122 patients with UBC, pathological stage pT1–pT4 treated with RC and pelvic lymph node dissection (PLND) during 2005–2011 at the Department of Urology, Linköping University Hospital. In the first study, we compared the results of preoperative PET/CT and conventional CT with the findings of postoperative histopathological evaluation of lymph nodes (LNs). In the second study we investigated the value of SNB technique for detecting pathological LNs during RC in patients with UBC. W also examined the significance of the primary tumor location in the bladder in predicting the site of LN metastases, and the prognostic significance of lympho-vascular invasion (LVI) and lymph node metastasis density (LNMD) on survival. In the third study, we investigate the clinical significance of macrophage infiltration (MI) in tumor stroma and macrophage-traits expression by tumor cells. In the fourth study, we investigate the cell cycle suppression proteins p53, p21, pRb, p16, p14 ARF as well as tumors proliferative protein Ki67 and DNA repair protein ERCC1 expression in cancer cells. The results were compared with clinical and pathological characteristics and outcome.Results: Prior to RC, PET/CT was used to detect LN metastasis in 54 patients. PET/CT had 41% sensitivity, 86% specificity, 58% PPV, and 76% NPV, whereas the corresponding figures for conventional CT were 41%, 89%, 64%, and 77%. SNB was performed during RC in 103 patients. A median number of 29 (range 7–68) nodes per patient were examined. SNs were detected in 83 out of 103 patients (81%). The sensitivity and specificity for detecting metastatic disease by SNB varied among LN stations, with average values of 67% -90%. LNMD or ≥8% and LVI were significantly related to shorter survival. In 103 patients, MI was high in 33% of cases, while moderate and low infiltration occurred in 42% and 25% of tumors respectively. Patients with tumors containing high and moderate compared to low MI had low rate of LN metastases (P=0.06) and improved survival (P=0.06), although not at significant level. The expression of different tumor suppression proteins was altered in 47-91% of the patients. There were no significant association between cancer specific survival (CSS) and any of the studied biomarkers. In case of altered p14ARF, ERCC1 or p21, CSS was low in case of low p53 immunostaining but increased in case of p53 accumulation, although not at a significant level, indicating a possible protective effect of p53 accumulation in these cases.Conclusion: PET/ CT provided no improvement over conventional CT in detection and localization of regional LN metastases in bladder cancer. It is possible to detect the SN but the technique is not a reliable for perioperative localization of LN metastases; however, LVI and LNMD at a cut-off level of 8% had significant prognostic values. MI in the tumor microenvironment but not CD163 expression in tumor cells seems to be synergistic with the immune response against urinary bladder cancer. Our results further indicate that altered p53 might have protective effect on survival in case of altered p14ARF, p21, or ERCC1 indicating an interaction between these biomarkers.
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| 7. |
- Loftås, Per, 1964-
(författare)
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Response to neoadjuvant treatment in rectal cancer surgery
- 2016
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Rectal cancer is one of the three most common malignancies in Sweden with an annual incidence of about 2000 cases. Current treatment consists of surgical resection of the rectum including the loco-regional lymph nodes in the mesorectum. In advanced cases, neoadjuvant chemo-radiotherapy (CRT) prior to the operative treatment reduces local recurrences and enables surgery. The neoadjuvant treatment can also eradicate the tumour completely, i.e. complete response. This research project was designed to investigate the effects of preoperative radiotherapy/ CRT and analyze methods to predict response to CRT.Study I investigated the expression of the FXYD-3 protein with immunohistochemistry in rectal cancer, with or without preoperative radiotherapy. The results from the total cohort showed that, strong FXYD-3 expression was correlated to infiltrative tumour growth (p = 0.02). In the radiotherapy group, strong FXYD-3 expression was related to an unfavourable prognosis (p = 0.02). Tumours with strong FXYD-3 expression had less tumour necrosis (p = 0.02) after radiotherapy. FXYD-3 expression in the primary tumour was increased compared to normal mucosa (p=0.008). We concluded that FXYD-3 expression was a prognostic factor in patients receiving preoperative radiotherapy for rectal cancer.Study II investigated FXYD-3 expression in tumours that developed local recurrences following surgery and compared this with expression in tumours that did not develop local recurrences. There was no difference in the expression of FXYD-3 between the group that developed local recurrences and the group that did not develop local recurrences. There was no difference in survival between those with strong or weak FXYD-3 expression. We concluded that this study could not confirm the findings from study 1 i.e. that FXYD-3 expression has prognostic significance in rectal cancer.Study III was a register-based study on the incidence and effects of complete response to neoadjuvant treatment. Eight per cent of the patients with adequate CRT to achieve complete response also had a complete histological response of the luminal tumor in the resected bowel. Sixteen per cent of that group had remaining lymph node metastases in the operative specimen. Chemotherapy together with radiotherapy doubled the chance of complete response in the luminal tumour. Patients with remaining lymph node metastases had a lower survival rate compared to those without. We concluded that residual nodal involvement after neoadjuvant treatment was an important factor for reduced survival after complete response in the luminal tumour.Study IV followed up the results from the previous study by re-evaluating magnetic resonance imaging (MRI)- images in patients with complete tumour response. Two experienced MRI radiologists performed blinded re-staging of post CRT MR- images from patients with complete response in the luminal tumour. One group with lymph node metastases and another one without were studied and the results compared with the pathology reports. The sensitivity, specificity, and positive and negative predicted values for correct staging of positive lymph nodes was 37%, 84%, 70% and 57%. The size of the largest lymph node (4.5 mm, p=0.04) seemed to indicate presence of a tumour positive lymph node. We concluded that MRI couldn’t correctly stage patients for lymph node metastases in patients with complete response to CRT in the luminal tumour.
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| 8. |
- Huvila, J., et al.
(författare)
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Combined ASRGL1 and p53 immunohistochemistry as an independent predictor of survival in endometrioid endometrial carcinoma
- 2018
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Ingår i: Gynecologic Oncology. - : Academic Press Inc.. - 0090-8258 .- 1095-6859. ; 149:1, s. 173-180
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Tidskriftsartikel (refereegranskat)abstract
- Objective: In clinical practise, prognostication of endometrial cancer is based on clinicopathological risk factors. The use of immunohistochemistry-based markers as prognostic tools is generally not recommended and a systematic analysis of their utility as a panel is lacking. We evaluated whether an immunohistochemical marker panel could reliably assess endometrioid endometrial cancer (EEC) outcome independent of clinicopathological information. Methods: A cohort of 306 EEC specimens was profiled using tissue microarray (TMA). Cost- and time-efficient immunohistochemical analysis of well-established tissue biomarkers (ER, PR, HER2, Ki-67, MLH1 and p53) and two new biomarkers (L1CAM and ASRGL1) was carried out. Statistical modelling with embedded variable selection was applied on the staining results to identify minimal prognostic panels with maximal prognostic accuracy without compromising generalizability. Results: A panel including p53 and ASRGL1 immunohistochemistry was identified as the most accurate predictor of relapse-free and disease-specific survival. Within this panel, patients were allocated into high- (5.9%), intermediate- (29.5%) and low- (64.6%) risk groups where high-risk patients had a 30-fold risk (P < 0.001) of dying of EEC compared to the low-risk group. Conclusions: P53 and ASRGL1 immunoprofiling stratifies EEC patients into three risk groups with significantly different outcomes. This simple and easily applicable panel could provide a useful tool in EEC risk stratification and guiding the allocation of treatment modalities.
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| 9. |
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| 10. |
- Aydogdu, Özgu, 1978, et al.
(författare)
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Urinary tract infection: Europe.
- 2011
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Ingår i: Guide to Pediatric Urology and Surgery in Clinical Practice. - 9781849963664 ; , s. 21-34
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 11. |
- Thulin, Helena, et al.
(författare)
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Defecation disturbances after cystectomy for urinary bladder cancer
- 2011
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Ingår i: BJU International. - : Blackwell Publishing Ltd. - 1464-4096 .- 1464-410X. ; 108:2, s. 196-203
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Tidskriftsartikel (refereegranskat)abstract
- What’s known on the subject? and What does the study add?Functional gastrointestinal symptoms and problems are common after radical cystectomy with urinary diversion. This study adds new important epidemiological data on this group of symptoms. OBJECTIVE: To describe and compare long-term defecation disturbances in patients who had undergone a cystectomy due to urinary bladder cancer with non-continent urostomies, continent reservoirs and orthotopic neobladder urinary diversions. PATIENTS AND METHODS: During their follow-up we attempted to contact all men and women aged 30–80 years who had undergone cystectomy and urinary diversion at seven Swedish hospitals. During a qualitative phase we identified defecation disturbances as a distressful symptom and included this item in a study-specific questionnaire together with free-hand comments. The patients completed the questionnaire at home. Outcome variables were dichotomized and the results are presented as relative risks with 95% confidence interval. RESULTS: The questionnaire was returned from 452 (92%) of 491 identified patients. Up to 30% reported problems with the physiological emptying process of stool (bowel movement, sensory rectal function, awareness of need for defecation, motoric rectal and anal function, straining ability). A sense of decreased straining capacity was reported by 20% of the men and women with non-continent urostomy and 14% and 8% of those with continent reservoirs and orthotopic neobladders, respectively. CONCLUSIONS: Of the cystectomized individuals 30% reported problems with the physiological emptying process of stool (bowel movement, sensory rectal function, awareness of need for defecation, motoric rectal and anal function, straining ability). Those wanting to improve the situation for bladder cancer survivors may consider communicating before surgery the possibility of stool-emptying problems, and asking about them after surgery.
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| 12. |
- Makvandi, Kianoush, et al.
(författare)
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Multiparametric magnetic resonance imaging allows non-invasive functional and structural evaluation of diabetic kidney disease
- 2022
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Ingår i: Clinical Kidney Journal. - : Oxford University Press (OUP). - 2048-8505 .- 2048-8513. ; 15:7, s. 1387-1402
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Tidskriftsartikel (refereegranskat)abstract
- Background We sought to develop a novel non-contrast multiparametric MRI (mpMRI) protocol employing several complementary techniques in a single scan session for a comprehensive functional and structural evaluation of diabetic kidney disease (DKD). Methods In the cross-sectional part of this prospective observational study, 38 subjects ages 18-79 years with type 2 diabetes and DKD [estimated glomerular filtration rate (eGFR) 15-60 mL/min/1.73 m(2)] and 20 age- and gender-matched healthy volunteers (HVs) underwent mpMRI. Repeat mpMRI was performed on 23 DKD subjects and 10 HVs. By measured GFR (mGFR), 2 DKD subjects had GFR stage G2, 16 stage G3 and 20 stage G4/G5. A wide range of MRI biomarkers associated with kidney haemodynamics, oxygenation and macro/microstructure were evaluated. Their optimal sensitivity, specificity and repeatability to differentiate diabetic versus healthy kidneys and categorize various stages of disease as well as their correlation with mGFR/albuminuria was assessed. Results Several MRI biomarkers differentiated diabetic from healthy kidneys and distinct GFR stages (G3 versus G4/G5); mean arterial flow (MAF) was the strongest predictor (sensitivity 0.94 and 1.0, specificity 1.00 and 0.69; P = .04 and .004, respectively). Parameters significantly correlating with mGFR were specific measures of kidney haemodynamics, oxygenation, microstructure and macrostructure, with MAF being the strongest univariate predictor (r = 0.92; P < .0001). Conclusions A comprehensive and repeatable non-contrast mpMRI protocol was developed that, as a single, non-invasive tool, allows functional and structural assessment of DKD, which has the potential to provide valuable insights into underlying pathophysiology, disease progression and analysis of efficacy/mode of action of therapeutic interventions in DKD.
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| 13. |
- Adolfsson, Jan, et al.
(författare)
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Clinical characteristics and primary treatment of prostate cancer in Sweden between 1996 and 2005 : Data from the national prostate cancer register in Sweden
- 2007
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Ingår i: Scandinavian Journal of Urology and Nephrology. - Stockholm : Taylor & Francis. - 0036-5599 .- 1651-2065. ; 41:6, s. 456-477
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Tidskriftsartikel (refereegranskat)abstract
- Objective. The incidence of prostate cancer is rising rapidly in Sweden and there is a need to better understand the pattern of diagnosis, tumor characteristics and treatment. Material and methods. Between 1996 and 2005, all new cases of adenocarcinoma of the prostate gland were intended to be registered in the National Prostate Cancer Register (NPCR). This register contains information on diagnosing unit, date of diagnosis, cause of diagnosis, tumor grade, tumor stage according to the TNM classification in force, serum prostate-specific antigen (PSA) levels at diagnosis and primary treatment given within the first 6 months after diagnosis. Results. In total, 72 028 patients were registered, comprising >97% of all pertinent incident cases of prostate cancer in the Swedish Cancer Register (SCR). During the study period there was a considerable decrease in median age at the time of diagnosis, a stage migration towards smaller tumors, a decrease in median serum PSA values at diagnosis, a decrease in the age-standardized incidence rate of men diagnosed with distant metastases or with a PSA level of >100 ng/ml at diagnosis and an increase in the proportion of tumors with Gleason score ≤6. Relatively large geographical differences in the median age at diagnosis and the age-standardized incidence of cases with category T1c tumors were observed. Treatment with curative intent increased dramatically and treatment patterns varied according to geographical region. In men with localized tumors and a PSA level of <20 ng/ml at diagnosis, expectant treatment was more commonly used in those aged ≥75 years than in those aged <75 years. Also, the pattern of endocrine treatment varied in different parts of Sweden. Conclusions. All changes in the register seen over time are consistent with increased diagnostic activity, especially PSA testing, resulting in an increased number of cases with early disease, predominantly tumors in category T1c. The patterns of diagnosis and treatment of prostate cancer vary considerably in different parts of Sweden. The NPCR continues to be an important source for research, epidemiological surveillance of the incidence, diagnosis and treatment of prostate cancer
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| 14. |
- Burgu, Berk, et al.
(författare)
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An unusual cause of infantile gynecomastia: sertoli cell tumor.
- 2011
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Ingår i: Journal of pediatric hematology/oncology. - 1536-3678. ; 33:3, s. 238-40
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Tidskriftsartikel (refereegranskat)abstract
- Prepubertal testicular masses are relatively rare. Sertoli cell tumors account for 2% of prepubertal testicular tumors and very few have occurred in the first decade of life. Gynecomastia can be seen in approximately 5% of patients with testicular mass. We present an 8-month-old boy admitted with bilateral gynecomastia and unilateral testicular mass.
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| 15. |
- Burgu, Berk, et al.
(författare)
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Pelvic reduction during pyeloplasty for antenatal hydronephrosis: does it affect outcome in ultrasound and nuclear scan postoperatively?
- 2010
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Ingår i: Urology. - : Elsevier BV. - 1527-9995 .- 0090-4295. ; 76:1, s. 169-74
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Tidskriftsartikel (refereegranskat)abstract
- To compare ultrasound (US) scan and nuclear renography findings in patients who underwent pyeloplasty with and without pelvic reduction in a randomized prospective study.A total of 42 patients, all prenatally diagnosed with unilateral hydronephrosis, were included. Hydronephrosis was confirmed postnatally. Twenty patients were randomly selected to undergo pyeloplasty with pelvic reduction and 22 underwent pelvis-sparing pyeloplasty. Patients were evaluated with mercaptoacetyltriglycine-3 scans on the sixth month and US scans on the first, third, and sixth months, postoperatively. Mean follow-up was 37 +/- 5.6 weeks. Statistical analyses were performed using chi-square test and significance was set as P <.05. Power analyses were performed by the NCSS-PASS program. Power value of 0.84 was calculated for a sample size of 42.The anteroposterior pelvic diameter decreased significantly in the pelvic reduction group compared with pelvis-sparing group in the first- and third-month US scans. However, the difference was not significant in the sixth month. The improvements in the US findings for the pelvis-sparing group match with those of the pelvic reduction group later in the postoperative period. Pelvic reduction significantly improved the renal washout time (T(1/2)) in mercaptoacetyltriglycine-3 renography when compared with pyeloplasty group without reduction at postoperative sixth month. Differential renal function was found to be unaffected from pelvic reduction.Resolution of anteroposterior diameter in US scan is more prominent in the pelvic reduction group at earlier stages of the postoperative period. Although T(1/2) decreases more prominently in the pelvic reduction group, the utility of this procedure is still indecisive. This feature can reveal possible surgical failures earlier and strengthen the values of US and renography postoperatively.
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| 16. |
- Li, Xiangyu, et al.
(författare)
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Classification of clear cell renal cell carcinoma based on PKM alternative splicing
- 2020
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Ingår i: Heliyon. - : Elsevier BV. - 2405-8440. ; 6:2
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Tidskriftsartikel (refereegranskat)abstract
- Clear cell renal cell carcinoma (ccRCC) accounts for 70-80% of kidney cancer diagnoses and displays high molecular and histologic heterogeneity. Hence, it is necessary to reveal the underlying molecular mechanisms involved in progression of ccRCC to better stratify the patients and design effective treatment strategies. Here, we analyzed the survival outcome of ccRCC patients as a consequence of the differential expression of four transcript isoforms of the pyruvate kinase muscle type (PKM). We first extracted a classification biomarker consisting of eight gene pairs whose within-sample relative expression orderings (REOs) could be used to robustly classify the patients into two groups with distinct molecular characteristics and survival outcomes. Next, we validated our findings in a validation cohort and an independent Japanese ccRCC cohort. We finally performed drug repositioning analysis based on transcriptomic expression profiles of drug-perturbed cancer cell lines and proposed that paracetamol, nizatidine, dimethadione and conessine can be repurposed to treat the patients in one of the subtype of ccRCC whereas chenodeoxycholic acid, fenoterol and hexylcaine can be repurposed to treat the patients in the other subtype.
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| 17. |
- Liedberg, Fredrik, et al.
(författare)
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Cumulative incidence of midline incisional hernia and its surgical treatment after radical cystectomy and urinary diversion for bladder cancer: A nation-wide population-based study
- 2021
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 16:2
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Tidskriftsartikel (refereegranskat)abstract
- Background and objective To study the cumulative incidence and surgical treatment of midline incisional hernia (MIH) after cystectomy for bladder cancer. Methods In the nationwide Bladder Cancer Data Base Sweden (BladderBaSe), cystectomy was performed in 5646 individuals. Cumulative incidence MIH and surgery for MIH were investigated in relation to age, gender, comorbidity, previous laparotomy and/or inguinal hernia repair, operative technique, primary/secondary cystectomy, postoperative wound dehiscence, year of surgery, and period-specific mean annual hospital cystectomy volume (PSMAV). Results Three years after cystectomy the cumulative incidence of MIH and surgery for MIH was 8% and 4%, respectively. The cumulative incidence MIH was 12%, 9% and 7% in patients having urinary diversion with continent cutaneous pouch, orthotopic neobladder and ileal conduit. Patients with postoperative wound dehiscence had a higher three-year cumulative incidence MIH (20%) compared to 8% without. The corresponding cumulative incidence surgery for MIH three years after cystectomy was 9%, 6%, and 4% for continent cutaneous, neobladder, and conduit diversion, respectively, and 11% for individuals with postoperative wound dehiscence (vs 4% without). Using multivariable Cox regression, secondary cystectomy (HR 1.3 (1.0-1.7)), continent cutaneous diversion (HR 1.9 (1.1-2.4)), robot-assisted cystectomy (HR 1.8 (1-3.2)), wound dehiscence (HR 3.0 (2.0-4.7)), cystectomy in hospitals with PSMAV 10-25 (HR 1.4 (1.0-1.9)), as well as cystectomy during later years (HRs 2.5-3.1) were all independently associated with increased risk of MIH. Conclusions The cumulative incidence of MIH was 8% three years postoperatively, and increase over time. Avoiding postoperative wound dehiscence after midline closure is important to decrease the risk of MIH.
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| 18. |
- Wallander, Marit, et al.
(författare)
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Patients with prostate cancer and androgen deprivation therapy have increased risk of fractures : a study from the fractures and fall injuries in the elderly cohort (FRAILCO)
- 2019
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Ingår i: Osteoporosis International. - : Springer. - 0937-941X .- 1433-2965. ; 30:1, s. 115-125
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Tidskriftsartikel (refereegranskat)abstract
- Summary: Osteoporosis is a common complication of androgen deprivation therapy (ADT). In this large Swedish cohort study consisting of a total of nearly 180,000 older men, we found that those with prostate cancer and ADT have a significantly increased risk of future osteoporotic fractures. Introduction: Androgen deprivation therapy (ADT) in patients with prostate cancer is associated to increased risk of fractures. In this study, we investigated the relationship between ADT in patients with prostate cancer and the risk of incident fractures and non-skeletal fall injuries both compared to those without ADT and compared to patients without prostate cancer. Methods: We included 179,744 men (79.1 ± 7.9 years (mean ± SD)) from the Swedish registry to which national directories were linked in order to study associations regarding fractures, fall injuries, morbidity, mortality and medications. We identified 159,662 men without prostate cancer, 6954 with prostate cancer and current ADT and 13,128 men with prostate cancer without ADT. During a follow-up of approximately 270,300 patient-years, we identified 10,916 incident fractures including 4860 hip fractures. Results: In multivariable Cox regression analyses and compared to men without prostate cancer, those with prostate cancer and ADT had increased risk of any fracture (HR 95% CI 1.40 (1.28–1.53)), hip fracture (1.38 (1.20–1.58)) and MOF (1.44 (1.28–1.61)) but not of non-skeletal fall injury (1.01 (0.90–1.13)). Patients with prostate cancer without ADT did not have increased risk of any fracture (0.97 (0.90–1.05)), hip fracture (0.95 (0.84–1.07)), MOF (1.01 (0.92–1.12)) and had decreased risk of non-skeletal fall injury (0.84 (0.77–0.92)). Conclusions: Patients with prostate cancer and ADT is a fragile patient group with substantially increased risk of osteoporotic fractures both compared to patients without prostate cancer and compared to those with prostate cancer without ADT. We believe that this must be taken in consideration in all patients with prostate cancer already at the initiation of ADT.
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| 19. |
- Xu, H., et al.
(författare)
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Excess protein intake relative to fiber and cardiovascular events in elderly men with chronic kidney disease
- 2016
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Ingår i: NMCD. Nutrition Metabolism and Cardiovascular Diseases. - : Elsevier BV. - 0939-4753 .- 1590-3729. ; 26:7, s. 597-602
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Tidskriftsartikel (refereegranskat)abstract
- Background and aims: The elevated cardiovascular (CVD) risk observed in chronic kidney disease (CKD) may be partially alleviated through diet. While protein intake may link to CVD events in this patient population, dietary fiber has shown cardioprotective associations. Nutrients are not consumed in isolation; we hypothesize that CVD events in CKD may be associated with dietary patterns aligned with an excess of dietary protein relative to fiber. Methods and Results: Prospective cohort study from the Uppsala Longitudinal Study of Adult Men. Included were 390 elderly men aged 70-71 years with CKD and without clinical history of CVD. Protein and fiber intake, as well as its ratio, were calculated from 7-day dietary records. Cardiovascular events were registered prospectively during a median follow-up of 9.1 (inter-quartile range, 4.5-10.7) years. The median dietary intake of protein and fiber was 66.7 (60.7-71.1) and 16.6 (14.5-19.1) g/day respectively and the protein-to-fiber intake ratio was 4.0 (3.5-4.7). Protein-to-fiber intake ratio was directly associated with serum C-reactive protein levels. During follow-up, 164 first-time CVD events occurred (incidence rate 54.5/1000 per year). Protein-fiber intake ratio was an independent risk factor for CVD events [adjusted hazard ratio, HR per standard deviation increase (95% confidence interval, CI) 1.33 (1.08, 1.64)]. Although in opposing directions, dietary protein [1.18 (0.97, 1.44)], dietary fiber alone [0.81 (0.64, 1.02)], were not significantly associated with CVD events. Conclusions: An excess of dietary protein relative to fiber intake was associated with the incidence of cardiovascular events in a homogeneous population of older men with CKD.
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| 20. |
- Xu, H., et al.
(författare)
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Lipophilic index, kidney function, and kidney function decline
- 2016
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Ingår i: NMCD. Nutrition Metabolism and Cardiovascular Diseases. - : Elsevier BV. - 0939-4753 .- 1590-3729. ; 31, s. 177-177
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Tidskriftsartikel (refereegranskat)abstract
- Background and aims: Unhealthy dietary fats are associated with faster kidney function decline. The cell membrane composition of phospholipid fatty acids (FAs) is a determinant of membrane fluidity and rheological properties. These properties, which have been linked to kidney damage, are thought to be reflected by the lipophilic index (LI). We prospectively investigated the associations of LI with kidney function and its decline. Methods and results: Observational study from the Prospective Investigation of Vasculature in Uppsala Seniors including 975 men and women with plasma phospholipid FAs composition and cystatin-C estimate glomerular filtration rate (eGFR). Of these, 780 attended reexamination after 5 years, and eGFR changes were assessed. Participants with a 5-year eGFR reduction >= 30% were considered chronic kidney disease (CKD) progressors (n = 198). LI was calculated as the sum of the products of the FA proportions with the respective FAs melting points. Blood rheology/viscosity measurements were performed in a random subsample of 559 subjects at baseline. Increased LI showed a statistically significant but overall weak association with blood, plasma viscosity (both Spearman rho = 0.16, p < 0.01), and erythrocyte deformability (rho = -0.09, p < 0.05). In cross-sectional analyses, LI associated with lower eGFR (regression coefficient 3.00 ml/min/1.73 m(2) 1-standard deviation (SD) increment in LI, 95% CI: -4.31, -1.69, p < 0.001). In longitudinal analyses, LI associated with a faster eGFR decline (-2.13 [95% CI -3.58, -0.69] ml/min/1.73 m(2), p < 0.01) and with 32% increased odds of CKD progression (adjusted OR 1.32 [95%, CI 1.05-1.65]). Conclusions: A high LI was associated with lower kidney function, kidney function decline, and CKD progression.
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| 21. |
- Andersson, John, 1978, et al.
(författare)
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Developing a multivariable prediction model of global health-related quality of life in patients treated for rectal cancer : a prospective study in five countries
- 2024
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Ingår i: International Journal of Colorectal Disease. - : Springer Nature. - 0179-1958 .- 1432-1262. ; 39
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Tidskriftsartikel (refereegranskat)abstract
- Purpose Rectal cancer and its treatment have a negative impact on health-related quality of life (HRQoL). If risk factors for sustained low HRQoL could be identified early, ideally before the start of treatment, individualised interventions could be identified and implemented to maintain or improve HRQoL. The study aimed to develop a multivariable prediction model for global HRQoL 12 months after rectal cancer treatment.Methods Within COLOR II, a randomised, multicentre, international trial of laparoscopic and open surgery for rectal cancer, a sub-study on HRQoL included 385 patients in 12 hospitals and five countries. The HRQoL study was optional for hospitals in the COLOR II trial. EORTC QLQ-C30 and EORTC QLQ-CR38 were analysed preoperatively and at 1 and 12 months postoperatively. In exploratory analyses, correlations between age, sex, fatigue, pain, ASA classification, complications, and symptoms after surgery to HRQoL were studied. Bivariate initial analyses were followed by multivariate regression models.Results Patient characteristics and clinical factors explained 4–10% of the variation in global HRQoL. The patient-reported outcomes from EORTC QLQ-C30 explained 55–65% of the variation in global HRQoL. The predominant predictors were fatigue and pain, which significantly impacted global HRQoL at all time points measured.Conclusion We found that fatigue and pain were two significant factors associated with posttreatment global HRQoL in patients treated for rectal cancer T1-T3 Nx. Interventions to reduce fatigue and pain could enhance global HRQoL after rectal cancer treatment.
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| 22. |
- Glimelius, Bengt, et al.
(författare)
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Persistent prevention of oxaliplatin-induced peripheral neuropathy using calmangafodipir (PledOx®) : a placebo-controlled randomised phase II study (PLIANT)
- 2018
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Ingår i: Acta Oncologica. - 0284-186X .- 1651-226X. ; 57:3, s. 393-402
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Oxaliplatin causes disabling acute and chronic peripheral neuropathy. We explored the preventive effects of calmangafodipir, mimicking the mitochondrial enzyme manganese superoxide dismutase, thereby protecting cells from oxidative stress, in a placebo-controlled, double-blinded randomised phase II study (ClinicalTrials.gov.NCT01619423) in patients with metastatic colorectal cancer (mCRC).Patient and methods: mCRC patients treated with modified FOLFOX-6 (folinic acid 200 mg/m2, 5-fluorouracil bolus 400 mg/m2, oxaliplatin 85 mg/m2 and 5-fluorouracil 2400 mg/m2 continuous infusion for 46 h) every fortnight for 8 cycles in first or second line were eligible. Calmangafodipir was given in a phase I dose-finding and in a phase II placebo-controlled study, as a 5-min infusion 10 min prior to oxaliplatin. Neurotoxicity was evaluated by the physician using the Oxaliplatin Sanofi Specific Scale and by the patient using the cold allodynia test and the Leonard scale.Results: Eleven patients were included in phase I without any detectable toxicity to calmangafodipir. In the phase II study, 173 patients were randomised to placebo (n = 60), calmangafodipir 2 µmol/kg (n = 57) and calmangafodipir 5 µmol/kg (n = 45, initially 10 µmol/kg, n = 11). Calmangafodipir-treated patients (all three doses pooled) had less physician graded neurotoxicity (odds ratio (90% confidence interval one-sided upper level) 0.62(1.15), p = .16), significantly less problems with cold allodynia (mean 1.6 versus 2.3, p < .05) and significantly fewer sensory symptoms in the Leonard scale (cycle 1–8 mean 1.9 versus 3.0, p < .05 and during follow-up after 3 and 6 months, mean 3.5 versus 7.3, p < .01). Response rate, progression-free and overall survival did not differ among groups.Conclusions: Calmangafodipir at a dose of 5 µmol/kg appears to prevent the development of oxaliplatin-induced acute and delayed CIPN without apparent influence on tumour outcomes.
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| 23. |
- Lönnbro-Widgren, Jennie, et al.
(författare)
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Treatment pattern in patients with idiopathic membranous nephropathy-practices in Sweden at the start of the millennium
- 2016
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Ingår i: Clinical Kidney Journal. - : Oxford University Press (OUP). - 2048-8505 .- 2048-8513. ; 9:2, s. 227-233
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Tidskriftsartikel (refereegranskat)abstract
- Background Idiopathic membranous nephropathy (MN) is one of the leading causes of nephrotic syndrome in adults and may result in end-stage renal disease (ESRD). In this retrospective study, we describe the outcomes and treatment patterns of patients with idiopathic MN in six nephrology clinics in the western part of Sweden. Methods Seventy-three consecutive patients with biopsy-proven MN in the years 2000-12 were classified as idiopathic, i.e. secondary forms were excluded. The patients were followed retrospectively for a mean period of 83 months and clinical data were collected through the medical files. Results A high proportion (88%) of the patients received supportive treatment with angiotensin-converting enzyme inhibition, angiotensin receptor blockade and/or statins. At the end of follow-up, 43 patients were in complete remission, 12 in partial remission, 10 patients had developed ESRD and 8 patients had on-going proteinuria. Fifty-one per cent of the patients received immunosuppressive therapy and the choice of therapy varied between and within the clinics. There was a tendency to initiate specific treatment at an early point instead of awaiting a possible spontaneous remission (21% of the patients), and non-recommended therapy such as corticosteroids only was used in a high proportion of these cases (47%). Conclusions Even though the treatment recommendations in idiopathic MN have not changed the last decade, the question of whom and when to treat seems to lead to uncertainty. Recent studies have presented promising results supporting the PLA2R antibody the predictive marker needed for this patient group. The diverse treatment approach presented in this study might have resulted in a worse outcome than expected. Hopefully, unnecessary exposure to immunosuppressive therapy or delayed treatment can be avoided through better support, education and treatment forums, and thus result in an improved outcome. © The Author 2016. Published by Oxford University Press on behalf of ERA-EDTA.
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| 24. |
- Morgell, Ann, et al.
(författare)
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Metabolic Characterization of Plasma and Cyst Fluid from Cystic Precursors to Pancreatic Cancer Patients Reveal Metabolic Signatures of Bacterial Infection
- 2021
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Ingår i: Journal of Proteome Research. - : American Chemical Society (ACS). - 1535-3907 .- 1535-3893. ; 20:5, s. 2725-2738
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Tidskriftsartikel (refereegranskat)abstract
- Pancreatic cancer is the seventh leading cause of cancer-related death worldwide, with a 5 year survival rate as low as 9%. One factor complicating the management of pancreatic cancer is the lack of reliable tools for early diagnosis. While up to 50% of the adult population has been shown to develop precancerous pancreatic cysts, limited and insufficient approaches are currently available to determine whether a cyst is going to progress into pancreatic cancer. Recently, we used metabolomics approaches to identify candidate markers of disease progression in patients diagnosed with intraductal papillary mucinous neoplasms (IPMNs) undergoing pancreatic resection. Here, we enrolled an independent cohort to verify the candidate markers from our previous study with orthogonal quantitative methods in plasma and cyst fluid from serous cystic neoplasm and IPMN (either low- or high-grade dysplasia or pancreatic ductal adenocarcinoma). We thus validated these markers with absolute quantitative methods through the auxilium of stable isotope-labeled internal standards in a new independent cohort. Finally, we identified novel markers of IPMN status and disease progression - including amino acids, carboxylic acids, conjugated bile acids, free and carnitine-conjugated fatty acids, purine oxidation products, and trimethylamine-oxide. We show that the levels of these metabolites of potential bacterial origin correlated with the degree of bacterial enrichment in the cyst, as determined by 16S RNA. Overall, our findings are interesting per se, owing to the validation of previous markers and identification of novel small molecule signatures of IPMN and disease progression. In addition, our findings further fuel the provoking debate as to whether bacterial infections may represent an etiological contributor to the development and severity of the disease in pancreatic cancer, in like fashion to other cancers (e.g., Helicobacter pylori and gastric cancer).
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| 25. |
- Skoog, Bengt, et al.
(författare)
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Short-term prediction of secondary progression in a sliding window: A test of a predicting algorithm in a validation cohort
- 2019
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Ingår i: Multiple Sclerosis Journal - Experimental, Translational and Clinical. - : SAGE Publications. - 2055-2173. ; 5:3
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: The Multiple Sclerosis Prediction Score (MSPS, www.msprediction.com) estimates, for any month during the course of relapsing–remitting multiple sclerosis (MS), the individual risk of transition to secondary progression (SP) during the following year. Objective: Internal verification of the MSPS algorithm in a derivation cohort, the Gothenburg Incidence Cohort (GIC, n = 144) and external verification in the Uppsala MS cohort (UMS, n = 145). Methods: Starting from their second relapse, patients were included and followed for 25 years. A matrix of MSPS values was created. From this matrix, a goodness-of-fit test and suitable diagnostic plots were derived to compare MSPS-calculated and observed outcomes (i.e. transition to SP). Results: The median time to SP was slightly longer in the UMS than in the GIC, 15 vs. 11.5 years (p = 0.19). The MSPS was calibrated with multiplicative factors: 0.599 for the UMS and 0.829 for the GIC; the calibrated MSPS provided a good fit between expected and observed outcomes (chi-square p = 0.61 for the UMS), which indicated the model was not rejected. Conclusion: The results suggest that the MSPS has clinically relevant generalizability in new cohorts, provided that the MSPS was calibrated to the actual overall SP incidence in the cohort.
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