| 11. |
- Vilhjalmsson, Dadi, et al.
(författare)
-
Compression anastomotic ring-locking procedure (CARP) is a safe and effective method for intestinal anastomoses following left-sided colonic resection.
- 2015
-
Ingår i: International Journal of Colorectal Disease. - : Springer Science and Business Media LLC. - 1432-1262 .- 0179-1958. ; 30:7, s. 969-975
-
Tidskriftsartikel (refereegranskat)abstract
- Compression anastomotic ring-locking procedure (CARP) is a novel procedure for creating colonic anastomoses. The surgical procedure allows perioperative quantification of the compression pressure between the intestinal ends within the anastomosis and postoperative monitoring of the anastomotic integrity. We have recently shown that CARP is a safe and effective method for colonic anastomoses in pigs, and the purpose of the present study was to evaluate CARP for colonic anastomoses in humans.
|
|
| 12. |
- Vilhjalmsson, Dadi, et al.
(författare)
-
The Compression Anastomotic Ring-Locking Procedure: A Novel Technique for Creating a Sutureless Colonic Anastomosis.
- 2015
-
Ingår i: European Surgical Research. - : S. Karger AG. - 0014-312X .- 1421-9921. ; 54:3-4, s. 139-147
-
Tidskriftsartikel (refereegranskat)abstract
- Background/Aim: Compression anastomoses might represent an improvement over traditional hand-sewn or stapled techniques. Herein, we describe a novel concept of sutureless colonic anastomosis named compression anastomotic ring-locking procedure (CARP). Materials and Methods: The surgical device consists of two anastomotic rings and their associated helping tools, facilitating the placement of the rings into the intestinal ends. Furthermore, four catheters are connected to the surgical device, allowing the evaluation of the anastomosis during and after surgery. A total of 31 pigs underwent a low colocolic anastomosis using the anastomotic rings. The compression pressure was measured perioperatively and up to 96 h after surgery. Anastomotic integrity and morphology were analyzed by use of radiology and histology, respectively. A long-term follow-up was conducted in a subgroup of pigs up to 108 days after surgery when the bursting pressure and stricture formation were examined. Results: All animals recovered uneventfully, and macroscopic examination revealed intact anastomoses without signs of pathological inflammation or adhesions. The perioperative compression pressure was inversely proportional to the gap size between the anastomotic rings. For example, an anastomotic gap of 1.5 mm created a colonic anastomosis with a perioperative compression pressure of 91 mbar, which remained constant for up to 48 h and resulted in a markedly increased compression pressure. Contrast infusion via the catheters effectively visualized the anastomoses, and no leakage was detected within the study. The surgical device was spontaneously evacuated from the intestines within 6 days after surgery. Histology showed collagen bridging of the anastomoses already 72 h after surgery. Long-term follow-up (54-108 days) revealed no stricture formation in the anastomoses, and the bursting pressure ranged from 120 to 235 mbar. The majority of bursts (10/12) occurred distant from the anastomoses. Conclusion: We conclude that the surgical device associated to CARP is safe and efficient for creating colonic anastomoses. Further studies in patients undergoing colorectal surgery are warranted. © 2014 S. Karger AG, Basel.
|
|
| 13. |
- Wang, Mei, et al.
(författare)
-
Determining breast cancer histological grade from RNA-sequencing data
- 2016
-
Ingår i: Breast Cancer Research. - Stockholm : Karolinska Institutet, Dept of Medical Epidemiology and Biostatistics. - 1465-542X.
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The histologic grade (HG) of breast cancer is an established prognostic factor. The grade is usually reported on a scale ranging from 1 to 3, where grade 3 tumours are the most aggressive. However, grade 2 is associated with an intermediate risk of recurrence, and carries limited information for clinical decision-making. Patients classified as grade 2 are at risk of both under- and over-treatment. METHODS: RNA-sequencing analysis was conducted in a cohort of 275 women diagnosed with invasive breast cancer. Multivariate prediction models were developed to classify tumours into high and low transcriptomic grade (TG) based on gene- and isoform-level expression data from RNA-sequencing. HG2 tumours were reclassified according to the prediction model and a recurrence-free survival analysis was performed by the multivariate Cox proportional hazards regression model to assess to what extent the TG model could be used to stratify patients. The prediction model was validated in N=487 breast cancer cases from the The Cancer Genome Atlas (TCGA) data set. Differentially expressed genes and isoforms associated with HGs were analysed using linear models. RESULTS: The classification of grade 1 and grade 3 tumours based on RNA-sequencing data achieved high accuracy (area under the receiver operating characteristic curve = 0.97). The association between recurrence-free survival rate and HGs was confirmed in the study population (hazard ratio of grade 3 versus 1 was 2.62 with 95 % confidence interval = 1.04-6.61). The TG model enabled us to reclassify grade 2 tumours as high TG and low TG gene or isoform grade. The risk of recurrence in the high TG group of grade 2 tumours was higher than in low TG group (hazard ratio = 2.43, 95 % confidence interval = 1.13-5.20). We found 8200 genes and 13,809 isoforms that were differentially expressed between HG1 and HG3 breast cancer tumours. CONCLUSIONS: Gene- and isoform-level expression data from RNA-sequencing could be utilised to differentiate HG1 and HG3 tumours with high accuracy. We identified a large number of novel genes and isoforms associated with HG. Grade 2 tumours could be reclassified as high and low TG, which has the potential to reduce over- and under-treatment if implemented clinically.
|
|
| 14. |
- Wang, Mei, et al.
(författare)
-
Development and Validation of a Novel RNA Sequencing-Based Prognostic Score for Acute Myeloid Leukemia
- 2018
-
Ingår i: Journal of the National Cancer Institute. - : OXFORD UNIV PRESS INC. - 0027-8874 .- 1460-2105. ; 110:10, s. 1094-1101
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Recent progress in sequencing technologies allows us to explore comprehensive genomic and transcriptomic information to improve the current European LeukemiaNet (ELN) system of acute myeloid leukemia (AML).Methods: We compared the prognostic value of traditional demographic and cytogenetic risk factors, genomic data in the form of somatic aberrations of 25 AML-relevant genes, and whole-transcriptome expression profiling (RNA sequencing) in 267 intensively treated AML patients (Clinseq-AML). Multivariable penalized Cox models (overall survival [OS]) were developed for each data modality (clinical, genomic, transcriptomic), together with an associated prognostic risk score.Results: Of the three data modalities, transcriptomic data provided the best prognostic value, with an integrated area under the curve (iAUC) of a time-dependent receiver operating characteristic (ROC) curve of 0.73. We developed a prognostic risk score (Clinseq-G) from transcriptomic data, which was validated in the independent The Cancer Genome Atlas AML cohort (RNA sequencing, n = 142, iAUC = 0.73, comparing the high-risk group with the low-risk group, hazard ratio [HR] OS = 2.42, 95% confidence interval [CI] = 1.51 to 3.88). Comparison between Clinseq-G and ELN score iAUC estimates indicated strong evidence in favor of the Clinseq-G model (Bayes factor = 26.78). The proposed model remained statistically significant in multivariable analysis including the ELN and other well-known risk factors (HRos = 2.34, 95% CI = 1.30 to 4.22). We further validated the Clinseq-G model in a second independent data set (n = 458, iAUC = 0.66, adjusted HROS = 2.02, 95% CI = 1.33 to 3.08; adjusted HREFS = 2.10, 95% CI = 1.42 to 3.12).Conclusions: Our results indicate that the Clinseq-G prediction model, based on transcriptomic data from RNA sequencing, outperforms traditional clinical parameters and previously reported models based on genomic biomarkers.
|
|
| 15. |
- Åström, Lennart
(författare)
-
Dose Escalation with High Dose Rate Brachytherapy or Protons in Curative Radiotherapy of Prostate Cancer
- 2018
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The aim of the thesis was to study the outcome and side effects after dose-escalated radiotherapy with high dose rate brachytherapy (HDR-BT) or proton beam therapy (PBT) boost in prostate cancer.The first cohorts of men in Sweden treated with either HDR-BT or PBT in combination with conventional photon beam therapy (2 Gray (Gy) fractions to 50 Gy) were analysed. The HDR-BT was given with two 10 Gy fractions, and the PBT with four fractions of 5 Gy. The analyses included 823 men in two HDR-BT cohorts, and 265 men in the PBT cohort. A large proportion of the cohorts, from 38% to 53%, were classified as high risk. After a follow-up between four and eleven years, both combinations showed low risks for relapse. The overall 5-year risk for PSA relapse was 0% for men with low risk. After PBT, the 5-year PSA relapse risk for intermediate and high risk were 5% and 26% respectively. After HDR-BT the 10-year risks for PSA relapse were 0%, 21% and 33% for low, intermediate, and high risk, respectively.The risk for early and late toxicity was low. Genitourinary (GU) toxicity was more frequent than gastrointestinal (GI) toxicity. GU toxicity may have a late onset and progress slowly with time after HDR-BT. The 5- and 10-year actuarial incidences of urethral stricture were 6% and 10% respectively after HDR-BT. With applied dose constraints to the urethra the 10-year risk was 5%. The actuarial prevalence of GI toxicity declined slowly with time after HDR-BT as well as after PBT.A PSA bounce after HDR-BT was seen in 26% of the patients, more frequent with younger age and lower Gleason score, and followed by a low risk for relapse.For dose-escalated radiotherapy with HDR-BT or PBT:long-term tumour control was achieved, not only for low- and intermediate risk, but also for the majority of high risk patients,a PSA bounce after HDR-BT was folled by a good prognosis,levels of late toxicity were low,genitourinary toxicity was more frequent than gastrointestinal toxicity,dose constraints to risk organs must be applied to minimise risks for late toxicity.
|
|
