Publications by authors named "B Th Björnsson"

187 Publications

Effects of long-term cortisol treatment on growth and osmoregulation of Atlantic salmon and brook trout.

Gen Comp Endocrinol 2021 Mar 29:113769. Epub 2021 Mar 29.

U.S. Geological Survey, Eastern Ecological Science Center, Conte Research Laboratory, Turners Falls, MA, USA; Department of Biology, University of Massachusetts, Amherst, MA 01003, USA.

Cortisol is the final product of the hypothalamic-pituitary-interrenal (HPI) axis and acts as a gluco- and mineralo-corticoid in fish. Long-term elevations of cortisol have been linked to reduced growth in fishes, but the mechanism(s) and relative sensitivities of species are still unclear. We carried out experiments to examine the relative effects of cortisol on growth and gill NKA activity in two salmonids: Atlantic salmon (Salmo salar) and brook trout (Salvelinus fontinalis). Treatment with intraperitoneal cortisol implants for 30 days resulted in reduced growth in both species, but with greater sensitivity to cortisol in brook trout. Gill NKA activity was strongly upregulated by cortisol in Atlantic salmon, and weakly upregulated in brook trout but with no statistically significant effect. Cortisol treatment resulted in reduced plasma levels of insulin-like growth factor I and increased plasma growth hormone levels in Atlantic salmon. Our results demonstrate that there are species differences in the sensitivity of growth and osmoregulation to cortisol, even among species in the same family (Salmonidae).
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http://dx.doi.org/10.1016/j.ygcen.2021.113769DOI Listing
March 2021

Reinforced versus standard stapler transection on postoperative pancreatic fistula in distal pancreatectomy: multicentre randomized clinical trial.

Br J Surg 2021 Jan 20. Epub 2021 Jan 20.

Division of Surgery, Department of Clinical Sciences, Intervention and Technology (CLINTECH), Karolinska Institutet at Centre for Digestive Diseases, Karolinska University Hospital, Stockholm, Sweden.

Background: Postoperative pancreatic fistula is the leading cause of morbidity after distal pancreatectomy. Strategies investigated to reduce the incidence have been disappointing. Recent data showed a reduction in postoperative pancreatic fistula with the use of synthetic mesh reinforcement of the staple line.

Methods: An RCT was conducted between May 2014 and February 2016 at four tertiary referral centres in Sweden. Patients scheduled for distal pancreatectomy were eligible. Enrolled patients were randomized during surgery to stapler transection with biological reinforcement or standard stapler transection. Patients were blinded to the allocation. The primary endpoint was the development of any postoperative pancreatic fistula. Secondary endpoints included morbidity, mortality, and duration of hospital stay.

Results: Some 107 patients were randomized and 106 included in an intention-to-treat analysis (56 in reinforced stapling group, 50 in standard stapling group). No difference was demonstrated in terms of clinically relevant fistulas (grade B and C): 6 of 56 (11 per cent) with reinforced stapling versus 8 of 50 (16 per cent) with standard stapling (P = 0.332). There was no difference between groups in overall postoperative complications: 45 (80 per cent) and 39 (78 per cent) in reinforced and standard stapling groups respectively (P = 0.765). Duration of hospital stay was comparable: median 8 (range 2-35) and 9 (2-114) days respectively (P = 0.541).

Conclusion: Biodegradable stapler reinforcement at the transection line of the pancreas did not reduce postoperative pancreatic fistula compared with regular stapler transection in distal pancreatectomy. Registration number: NCT02149446 (http://www.clinicaltrials.gov).
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http://dx.doi.org/10.1093/bjs/znaa113DOI Listing
January 2021

Preoperative portal vein or portal and hepatic vein embolization: DRAGON collaborative group analysis.

Br J Surg 2021 Mar 1. Epub 2021 Mar 1.

Institute of Physiology, University of Zurich, Zurich, Switzerland.

Background: The extent of liver resection for tumours is limited by the expected functional reserve of the future liver remnant (FRL), so hypertrophy may be induced by portal vein embolization (PVE), taking 6 weeks or longer for growth. This study assessed the hypothesis that simultaneous embolization of portal and hepatic veins (PVE/HVE) accelerates hypertrophy and improves resectability.

Methods: All centres of the international DRAGON trials study collaborative were asked to provide data on patients who had PVE/HVE or PVE on 2016-2019 (more than 5 PVE/HVE procedures was a requirement). Liver volumetry was performed using OsiriX MD software. Multivariable analysis was performed for the endpoints of resectability rate, FLR hypertrophy and major complications using receiver operating characteristic (ROC) statistics, regression, and Kaplan-Meier analysis.

Results: In total, 39 patients had undergone PVE/HVE and 160 had PVE alone. The PVE/HVE group had better hypertrophy than the PVE group (59 versus 48 per cent respectively; P = 0.020) and resectability (90 versus 68 per cent; P = 0.007). Major complications (26 versus 34 per cent; P = 0.550) and 90-day mortality (3 versus 16 per cent respectively, P = 0.065) were comparable. Multivariable analysis confirmed that these effects were independent of confounders.

Conclusion: PVE/HVE achieved better FLR hypertrophy and resectability than PVE in this collaborative experience.
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http://dx.doi.org/10.1093/bjs/znaa149DOI Listing
March 2021

Malignancy in elective cholecystectomy due to gallbladder polyps or thickened gallbladder wall: a single-centre experience.

Scand J Gastroenterol 2021 Apr 16;56(4):458-462. Epub 2021 Feb 16.

Department of Surgery, Linköping University, Linköping, Sweden.

Introduction: Gallbladder cancer is a rare but aggressive malignancy. Surgical resection is recommended for gallbladder polyps ≥10 mm. For gallbladder wall thickening, resection is recommended if malignancy cannot be excluded. The incidence of gallbladder malignancy after cholecystectomy with indications of polyps or wall thickening in the Swedish population is not known.

Material/methods: A retrospective study was performed at Linköping University Hospital and included patients who underwent cholecystectomy 2010 - 2018. All cholecystectomies performed due to gallbladder polyps or gallbladder wall thickening without other preoperative malignant signs were identified. Preoperative radiological examinations were re-analysed by a single radiologist. Medical records and histopathology reports were analysed.

Results: In all, 102 patients were included, of whom 65 were diagnosed with gallbladder polyps and 37 with gallbladder wall thickening. In each group, one patient (1.5% and 2.7% in each group) had gallbladder malignancy ≥ pT1b.Two (3.1%) and three (8.1%) patients with gallbladder malignancy < T1b were identified in each group.

Discussion/conclusion: This study indicates that the incidence of malignancy is low without other malignant signs beyond gallbladder polyps and/or gallbladder wall thickening. We propose that these patients should be discussed at a multidisciplinary tumour board. If the polyp is 10-15 mm or if the gallbladder wall is thickened but no other malignant signs are observed, cholecystectomy can be safely performed by an experienced general surgeon at a general surgery unit. If the histopathology indicates ≥ pT1b, the patient should be referred immediately to a hepatobiliary centre for liver and lymph node resection.
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http://dx.doi.org/10.1080/00365521.2021.1884895DOI Listing
April 2021

How should liver hypertrophy be stimulated? A comparison of upfront associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) and portal vein embolization (PVE) with rescue possibility.

Hepatobiliary Surg Nutr 2021 Jan;10(1):1-8

Department of Surgery and Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.

Background: The role of associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) in comparison to portal vein embolization (PVE) is debated. The aim of this study was to compare successful resection rates (RR) with upfront ALPPS PVE with rescue ALPPS on demand and to compare the hypertrophy of the liver between ALPPS and PVE plus subsequent rescue ALPPS.

Methods: A retrospective analysis of all patients treated with PVE for colorectal liver metastasis (CRLM) or ALPPS (any diagnosis, rescue ALPPS included) at five Scandinavian university hospitals during the years 2013-2016 was conducted. A Chi-square test and a Mann-Whitney U test were used to assess the difference between the groups. A successful RR was defined as liver resection without a 90-day mortality.

Results: A total of 189 patients were included. Successful RR was in 84.5% of the patients with ALPPS upfront and in 73.3% of the patients with PVE and rescue ALPPS on demand (P=0.080). The hypertrophy of the future liver remnants (FLRs) with ALPPS upfront was 71% (48-97%) compared to 96% (82-113%) after PVE and rescue ALPPS (P=0.010).

Conclusions: Upfront ALPPS offers a somewhat higher successful RR than PVE with rescue ALPPS on demand. The sequential combination of PVE and ALPPS leads to a higher overall degree of hypertrophy than upfront ALPPS.
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http://dx.doi.org/10.21037/hbsn.2019.10.36DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7867725PMC
January 2021

Portal vein embolization with N-butyl cyanoacrylate glue is superior to other materials: a systematic review and meta-analysis.

Eur Radiol 2021 Jan 26. Epub 2021 Jan 26.

Department of Surgery and Clinical and Experimental Medicine, University Hospital of Linköping, Linköping, Sweden.

Objectives: It remains uncertain which embolization material is best for portal vein embolization (PVE). We investigated the various materials for effectiveness in inducing future liver remnant (FLR) hypertrophy, technical and growth success rates, and complication and resection rates.

Methods: A systematic review from 1998 to 2019 on embolization materials for PVE was performed on Pubmed, Embase, and Cochrane. FLR growth between the two most commonly used materials was compared in a random effects meta-analysis. In a separate analysis using local data (n = 52), n-butyl cyanoacrylate (NBCA) was compared with microparticles regarding costs, radiation dose, and procedure time.

Results: In total, 2896 patients, 61.0 ± 4.0 years of age and 65% male, from 51 papers were included in the analysis. In 61% of the patients, either NBCA or microparticles were used for embolization. The remaining were treated with ethanol, gelfoam, or sclerosing agents. The FLR growth with NBCA was 49.1% ± 29.7 compared to 42.2% ± 40 with microparticles (p = 0.037). The growth success rate with NBCA vs microparticles was 95.3% vs 90.7% respectively (p < 0.001). There were no differences in major complications between NBCA and microparticles. In the local analysis, NBCA (n = 41) entailed shorter procedure time and reduced fluoroscopy time (p < 0.001), lower radiation exposure (p < 0.01), and lower material costs (p < 0.0001) than microparticles (n = 11).

Conclusion: PVE with NBCA seems to be the best choice when combining growth of the FLR, procedure time, radiation exposure, and costs.

Key Points: • The meta-analysis shows that n-butyl cyanoacrylate (NBCA) is superior to microparticles regarding hypertrophy of the future liver remnant, 49.1% ± 29.7 vs 42.2% ± 40.0 (p = 0.037). • There is no significant difference in major complication rates for portal vein embolization using NBCA, 4% (24/681), compared with microparticles, 5% (25/494) (p > 0.05). • Local data shows a shorter procedure time, 215 vs 348 mins from arrival to departure at the interventional radiology unit, and fluoroscopy time, 43 vs 96 mins (p < 0.001), lower radiation dosage, 573 vs 1287 Gycm (p < 0.01), and costs, €816 vs €4233 (p < 0.0001) for NBCA compared to microparticles.
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http://dx.doi.org/10.1007/s00330-020-07685-wDOI Listing
January 2021

Laparoscopic versus open extended radical left pancreatectomy for pancreatic ductal adenocarcinoma: an international propensity-score matched study.

Surg Endosc 2021 Jan 4. Epub 2021 Jan 4.

Department of Surgery, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, Meibergdreef, 91100 AZ, Amsterdam, The Netherlands.

Background: A radical left pancreatectomy in patients with pancreatic ductal adenocarcinoma (PDAC) may require extended, multivisceral resections. The role of a laparoscopic approach in extended radical left pancreatectomy (ERLP) is unclear since comparative studies are lacking. The aim of this study was to compare outcomes after laparoscopic vs open ERLP in patients with PDAC.

Methods: An international multicenter propensity-score matched study including patients who underwent either laparoscopic or open ERLP (L-ERLP; O-ERLP) for PDAC was performed (2007-2015). The ISGPS definition for extended resection was used. Primary outcomes were overall survival, margin negative rate (R0), and lymph node retrieval.

Results: Between 2007 and 2015, 320 patients underwent ERLP in 34 centers from 12 countries (65 L-ERLP vs. 255 O-ERLP). After propensity-score matching, 44 L-ERLP could be matched to 44 O-ERLP. In the matched cohort, the conversion rate in L-ERLP group was 35%. The L-ERLP R0 resection rate (matched cohort) was comparable to O-ERLP (67% vs 48%; P = 0.063) but the lymph node yield was lower for L-ERLP than O-ERLP (median 11 vs 19, P = 0.023). L-ERLP was associated with less delayed gastric emptying (0% vs 16%, P = 0.006) and shorter hospital stay (median 9 vs 13 days, P = 0.005), as compared to O-ERLP. Outcomes were comparable for additional organ resections, vascular resections (besides splenic vessels), Clavien-Dindo grade ≥ III complications, or 90-day mortality (2% vs 2%, P = 0.973). The median overall survival was comparable between both groups (19 vs 20 months, P = 0.571). Conversion did not worsen outcomes in L-ERLP.

Conclusion: The laparoscopic approach may be used safely in selected patients requiring ERLP for PDAC, since morbidity, mortality, and overall survival seem comparable, as compared to O-ERLP. L-ERLP is associated with a high conversion rate and reduced lymph node yield but also with less delayed gastric emptying and a shorter hospital stay, as compared to O-ERLP.
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http://dx.doi.org/10.1007/s00464-020-08206-yDOI Listing
January 2021

Minimally invasive versus open distal pancreatectomy: an individual patient data meta-analysis of two randomized controlled trials.

HPB (Oxford) 2021 Mar 27;23(3):323-330. Epub 2020 Nov 27.

Department of Surgery and Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.

Background: Minimally invasive distal pancreatectomy (MIDP) has been suggested to reduce postoperative outcomes as compared to open distal pancreatectomy (ODP). Recently, the first randomized controlled trials (RCTs) comparing MIDP to ODP were published. This individual patient data meta-analysis compared outcomes after MIDP versus ODP combining data from both RCTs.

Methods: A systematic literature search was performed to identify RCTs on MIDP vs. ODP, and individual patient data were harmonized. Primary endpoint was the rate of major (Clavien-Dindo ≥ III) complications. Sensitivity analyses were performed in high-risk subgroups.

Results: A total of 166 patients from the LEOPARD and LAPOP RCTs were included. The rate of major complications was 21% after MIDP vs. 35% after ODP (adjusted odds ratio 0.54; p = 0.148). MIDP significantly reduced length of hospital stay (6 vs. 8 days, p = 0.036), and delayed gastric emptying (4% vs. 16%, p = 0.049), as compared to ODP. A trend towards higher rates of postoperative pancreatic fistula was observed after MIDP (36% vs. 28%, p = 0.067). Outcomes were comparable in high-risk subgroups.

Conclusion: This individual patient data meta-analysis showed that MIDP, when performed by trained surgeons, may be regarded as the preferred approach for distal pancreatectomy. Outcomes are improved after MIDP as compared to ODP, without obvious downsides in high-risk subgroups.
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http://dx.doi.org/10.1016/j.hpb.2020.10.022DOI Listing
March 2021

Response to Comment on "ALPPS Improves Survival Compared With TSH in Patients Affected of CRLM - It Is Time to Entry the IDEAL Stage 4?"

Ann Surg 2020 Nov 23. Epub 2020 Nov 23.

Department of Surgery and Clinical and Experimental Medicine, Linköping University, Linköping, Sweden Department of Hepato-Pancreato-Biliary Surgery, Oslo University Hospital, Oslo, Norway Department of Surgical Gastroenterology and Transplantation, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark Department of Clinical Science, Intervention and Technology, Division of Surgery, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden Department of Surgery, Skane University Hospital, Lund, Sweden Department of Surgical Gastroenterology and Transplantation, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark Department of Hepato-Pancreato-Biliary Surgery, Oslo University Hospital, Oslo, Norway Department of Surgery, Akademiska University Hospital, Uppsala, Sweden Department of Surgery and Clinical and Experimental Medicine, Linköping University, Linköping, Sweden Department of Transplantation and Liver Surgery, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden Department of Surgery and Clinical and Experimental Medicine, Linköping University, Linköping, Sweden Department of Surgery and Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.

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http://dx.doi.org/10.1097/SLA.0000000000004357DOI Listing
November 2020

Clinical Outcomes after Total Pancreatectomy: A Prospective Multicenter Pan-European Snapshot Study.

Ann Surg 2020 Nov 9. Epub 2020 Nov 9.

Department of General and Digestive Surgery, University Hospital of Guadalajara, Guadalajara, Spain.

Objective: To assess outcomes among patients undergoing total pancreatectomy (TP) including predictors for complications and in-hospital mortality.

Background: Current studies on TP mostly originate from high-volume centers and span long time periods and therefore may not reflect daily practice.

Methods: This prospective pan-European snapshot study included patients who underwent elective (primary or completion) TP in 43 centers in 16 European countries (June 2018-June 2019). Subgroup analysis included cut-off values for annual volume of pancreatoduodenectomies (<60 vs. ≥60). Predictors for major complications and in-hospital mortality were assessed in multivariable logistic regression.

Results: In total, 277 patients underwent TP, mostly for malignant disease (73%). Major postoperative complications occurred in 70 patients (25%). Median hospital stay was 12 days (IQR 9-18) and 40 patients were readmitted (15%). In-hospital mortality was 5% and 90-day mortality 8%. In the subgroup analysis, in-hospital mortality was lower in patients operated in centers with ≥60 pancreatoduodenectomies compared < 60 (4% vs. 10%, p = 0.046). In multivariable analysis, annual volume < 60 pancreatoduodenectomies (OR 3.78, 95%CI 1.18-12.16, p = 0.026), age (OR 1.07, 95%CI 1.01-1.14, p = 0.046), and estimated blood loss ≥2L (OR 11.89, 95%CI 2.64-53.61, p = 0.001) were associated with in-hospital mortality. ASA ≥3 (OR 2.87, 95%CI 1.56-5.26, p = 0.001) and estimated blood loss ≥2L (OR 3.52, 95%CI 1.25-9.90, p = 0.017) were associated with major complications.

Conclusion: This pan-European prospective snapshot study found a 5% in-hospital after TP. The identified predictors for mortality, including low-volume centers, age, and increased blood loss, may be used to improve outcomes.
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http://dx.doi.org/10.1097/SLA.0000000000004551DOI Listing
November 2020

Visualization of spherical aberration using an optically levitated droplet as a light source.

Opt Express 2020 Oct;28(21):30410-30422

Optical aberrations can greatly distort the image created by an optical element. Several aberrations can affect the image simultaneously and discerning or visualizing specific aberrations can be difficult. By making use of an optically levitated droplet as a light source, we have visualized the spherical aberration and coma of a lens. The droplet approximates a point source in the ray optic regime but, at the same time, creates a diffraction pattern in the far-field region similar to that used in the Ronchi test. When focused by a lens, this micro double point source creates patterns that resemble comets, barreling, hyperbolic triangles, and, most strikingly, a spider. We show how all these patterns are a consequence of spherical aberration and coma. The Zernike polynomials were used to quantify the value of several individual aberrations by comparing them to patterns resulting from numerical simulations.
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http://dx.doi.org/10.1364/OE.402759DOI Listing
October 2020

Photoperiodic regulation of pituitary thyroid-stimulating hormone and brain deiodinase in Atlantic salmon.

Mol Cell Endocrinol 2021 01 15;519:111056. Epub 2020 Oct 15.

U.S. Geological Survey, Leetown Science Center, Conte Anadromous Fish Research Laboratory, Turners Falls, MA, USA; Department of Biology, University of Massachusetts, Amherst, MA, USA. Electronic address:

Seasonal timing is important for many critical life history events of vertebrates, and photoperiod is often used as a reliable seasonal cue. In mammals and birds, it has been established that a photoperiod-driven seasonal clock resides in the brain and pituitary, and is driven by increased levels of pituitary thyroid stimulating hormone (TSH) and brain type 2 iodothyronine deiodinase (DIO2), which leads to local increases in triiodothyronine (T). In order to determine if a similar mechanism occurs in fish, we conducted photoperiod manipulations in anadromous (migratory) Atlantic salmon (Salmo salar) that use photoperiod to time the preparatory development of salinity tolerance which accompanies downstream migration in spring. Changing daylength from short days (light:dark (LD) 10:14) to long days (LD 16:8) for 20 days increased gill Na/K-ATPase (NKA) activity, gill NKAα1b abundance and plasma growth hormone (GH) levels that normally accompany increased salinity tolerance of salmon in spring. Long-day exposure resulted in five-fold increases in pituitary tshβb mRNA levels after 10 days and were sustained for at least 20 days. tshβb mRNA levels in the saccus vasculosus were low and not influenced by photoperiod. Increased daylength resulted in significant increases in dio2b mRNA levels in the hypothalamus and midbrain/optic tectum regions of the brain. The results are consistent with the presence of a photoperiod-driven seasonal clock in fish which involves pituitary TSH, brain DIO2 and the subsequent production of T, supporting the hypothesis that this is a common feature of photoperiodic regulation of seasonality in vertebrates.
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http://dx.doi.org/10.1016/j.mce.2020.111056DOI Listing
January 2021

Clinical characteristics and blood/serum bound prognostic biomarkers in advanced pancreatic cancer treated with gemcitabine and nab-paclitaxel.

BMC Cancer 2020 Oct 2;20(1):950. Epub 2020 Oct 2.

Department of Oncology and Department of Biomedical and Clinical Sciences, Linköping University, 58183, Linköping, Sweden.

Background: In recent years treatment options for advanced pancreatic cancer have markedly improved, and a combination regimen of gemcitabine and nab-paclitaxel is now considered standard of care in Sweden and elsewhere. Nevertheless, a majority of patients do not respond to treatment. In order to guide the individual patient to the most beneficial therapeutic strategy, simple and easily available prognostic and predictive markers are needed.

Methods: The potential prognostic value of a range of blood/serum parameters, patient-, and tumour characteristics was explored in a retrospective cohort of 75 patients treated with gemcitabine/nab-paclitaxel (Gem/NabP) for advanced pancreatic ductal adenocarcinoma (PDAC) in the South Eastern Region of Sweden. Primary outcome was overall survival (OS) while progression free survival (PFS) was the key secondary outcome.

Result: Univariable Cox regression analysis revealed that high baseline serum albumin (> 37 g/L) and older age (> 65) were positive prognostic markers for OS, and in multivariable regression analysis both parameters were confirmed to be independent prognostic variables (HR 0.48, p = 0.023 and HR = 0.47, p = 0.039,). Thrombocytopenia at any time during the treatment was an independent predictor for improved progression free survival (PFS) but not for OS (HR 0.49, p = 0.029, 0.54, p = 0.073), whereas thrombocytopenia developed under cycle 1 was neither related with OS nor PFS (HR 0.87, p = 0.384, HR 1.04, p = 0.771). Other parameters assessed (gender, tumour stage, ECOG performance status, myelosuppression, baseline serum CA19-9, and baseline serum bilirubin levels) were not significantly associated with survival.

Conclusion: Serum albumin at baseline is a prognostic factor with palliative Gem/NabP in advanced PDAC, and should be further assessed as a tool for risk stratification. Older age was associated with improved survival, which encourages further studies on the use of Gem/NabP in the elderly.
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http://dx.doi.org/10.1186/s12885-020-07426-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7530950PMC
October 2020

Cortisol regulates insulin-like growth-factor binding protein (igfbp) gene expression in Atlantic salmon parr.

Mol Cell Endocrinol 2020 12 21;518:110989. Epub 2020 Aug 21.

U.S. Geological Survey, Leetown Science Center, Conte Anadromous Fish Research Laboratory, One Migratory Way, Turners Falls, MA, 01376, USA.

The growth hormone (Gh)/insulin-like growth-factor (Igf)/Igf binding protein (Igfbp) system regulates growth and osmoregulation in salmonid fishes, but how this system interacts with other endocrine systems is largely unknown. Given the well-documented consequences of mounting a glucocorticoid stress response on growth, we hypothesized that cortisol inhibits anabolic processes by modulating the expression of hepatic igfbp mRNAs. Atlantic salmon (Salmo salar) parr were implanted intraperitoneally with cortisol implants (0, 10, and 40 μg g body weight) and sampled after 3 or 14 days. Cortisol elicited a dose-dependent reduction in specific growth rate (SGR) after 14 days. While plasma Gh and Igf1 levels were unchanged, hepatic igf1 mRNA was diminished and hepatic igfbp1b1 and -1b2 were stimulated by the high cortisol dose. Plasma Igf1 was positively correlated with SGR at 14 days. Hepatic gh receptor (ghr), igfbp1a, -2a, -2b1, and -2b2 levels were not impacted by cortisol. Muscle igf2, but not igf1 or ghr, levels were stimulated at 3 days by the high cortisol dose. As both cortisol and the Gh/Igf axis promote seawater (SW) tolerance, and particular igfbps respond to SW exposure, we also assessed whether cortisol coordinates the expression of branchial igfbps and genes associated with ion transport. Cortisol stimulated branchial igfbp5b2 levels in parallel with Na/K-ATPase (NKA) activity and nka-α1b, Na/K/2Cl-cotransporter 1 (nkcc1), and cystic fibrosis transmembrane regulator 1 (cftr1) mRNA levels. The collective results indicate that cortisol modulates the growth of juvenile salmon via the regulation of hepatic igfbp1s whereas no clear links between cortisol and branchial igfbps previously shown to be salinity-responsive could be established.
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http://dx.doi.org/10.1016/j.mce.2020.110989DOI Listing
December 2020

Author response to: Comment on: The LAPOP trial of laparoscopic or open distal pancreatectomy.

Br J Surg 2020 08 11;107(9):e356. Epub 2020 Jul 11.

Department of Surgery and Clinical and Experimental Medicine, Linköping University, Linköping.

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http://dx.doi.org/10.1002/bjs.11775DOI Listing
August 2020

In the Shadows of Patients with Upper Gastrointestinal Cancer: An Interview Study with Next of Kin about Their Experiences Participating in Surgical Cancer Care.

Clin Nurs Res 2020 11 10;29(8):579-586. Epub 2020 Jul 10.

Linköping University, Linköping, Sweden.

The study aimed to explore the experiences of participation among the next of kin of patients who had surgery for upper abdominal tumours. This study had a qualitative research design and data were analysed by thematic analysis. Eleven qualitative interviews were conducted with next of kin to patients who had surgery for liver, bile duct or pancreatic malignancy. The following themes emerged: and Next of kin were a central part of their loved one's care but often in the shadows. The next of kin described how they were not always invited and often they had to struggle to get involved. Next of kin often have a major psychosocial role to supporting the patient during and after discharge, and therefore need to be invited and involved in the whole care process.
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http://dx.doi.org/10.1177/1054773820940873DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7557747PMC
November 2020

Iterative reconstruction algorithm improves the image quality without affecting quantitative measurements of computed tomography perfusion in the upper abdomen.

Eur J Radiol Open 2020 3;7:100243. Epub 2020 Jul 3.

Department of Surgery in Linköping, and Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden.

Objective: To investigate differences between reconstruction algorithms in quantitative perfusion values and time-attenuation curves in computed tomography perfusion (CTP) examinations of the upper abdomen.

Methods: Twenty-six CTP examinations were reconstructed with filtered back projection and an iterative reconstruction algorithm, advanced modeled iterative reconstruction (ADMIRE), with different levels of noise-reduction strength. Using the maximum-slope model, quantitative measurements were obtained: blood flow (mL/min/100 mL), blood volume (mL/100 mL), time to peak (s), arterial liver perfusion (mL/100 mL/min), portal venous liver perfusion (mL/100 mL/min), hepatic perfusion index (%), temporal maximum intensity projection (Hounsfield units (HU)) and temporal average HU. Time-attenuation curves for seven sites (left liver lobe, right liver lobe, hepatocellular carcinoma, spleen, gastric wall, pancreas, portal vein) were obtained. Mixed-model analysis was used for statistical evaluation. Image noise and the signal:noise ratio (SNR) were compared between four reconstructions, and statistical analysis of these reconstructions was made with a related-samples Friedman's two-way analysis of variance by ranks test.

Results: There were no significant differences for quantitative measurements between the four reconstructions for all tissues. There were no significant differences between the AUC values of the time-attenuation curves between the four reconstructions for all tissues, including three automatic measurements (portal vein, aorta, spleen). There was a significant difference in image noise and SNR between the four reconstructions.

Conclusions: ADMIRE did not affect the quantitative measurements or time-attenuation curves of tissues in the upper abdomen. The image noise was lower, and the SNR higher, for iterative reconstructions with higher noise-reduction strengths.
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http://dx.doi.org/10.1016/j.ejro.2020.100243DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7334814PMC
July 2020

Response to comment on "ALPPS Improves Survival Compared With TSH in Patients Affected of CRLM: Survival Analysis From the Randomized Controlled Trial LIGRO-Metastatic Tumor Burden in the Future Liver Remnant for Decision-making of Staged Hepatectomy".

Ann Surg 2020 Jun 24. Epub 2020 Jun 24.

Department of Surgery and Clinical and Experimental Medicine, Linköping University, Sweden Department of Hepato-Pancreato-Biliary Surgery, Oslo University Hospital, Norway Department of Surgical Gastroenterology and Transplantation, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark Department of Clinical Science, Intervention and Technology, Division of Surgery, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden Department of Surgery, Skane University Hospital, Lund, Sweden Department of Surgical Gastroenterology and Transplantation, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark Department of Hepato-Pancreato-Biliary Surgery, Oslo University Hospital, Norway Department of Surgery, Akademiska University Hospital, Uppsala, Sweden Department of Surgery and Clinical and Experimental Medicine, Linköping University, Sweden Department of Transplantation and Liver Surgery, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. Department of Surgery and Clinical and Experimental Medicine, Linköping University, Sweden Department of Surgery and Clinical and Experimental Medicine, Linköping University, Sweden.

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http://dx.doi.org/10.1097/SLA.0000000000004014DOI Listing
June 2020

Author response to: Comment on: Comparison of the duration of hospital stay after laparoscopic or open distal pancreatectomy: randomized controlled trial.

Br J Surg 2020 07 23;107(8):e279. Epub 2020 May 23.

Department of Surgery and Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.

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http://dx.doi.org/10.1002/bjs.11681DOI Listing
July 2020

Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy (ALPPS) procedure for colorectal liver metastasis.

Int J Surg 2020 Oct 16;82S:103-108. Epub 2020 Apr 16.

Division of Surgery, Miguel Servet University Hospital and University of Zaragoza School of Medicine, Zaragoza, Spain.

Since first described, Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy (ALPPS) has garnered boisterous praise and fervent criticism. Its rapid adoption and employment for a variety of indications resulted in high perioperative morbidity and mortality. However recent risk stratification, refinement of technique to reduce the impact of stage I and progression along the learning curve have resulted in improved outcomes. The first randomized trial comparing ALPPS to two stage hepatectomy (TSH) for colorectal liver metastases (CRLM) was recently published demonstrating comparable perioperative morbidity and mortality with improved resectability and survival following ALPPS. In this review, as ALPPS enters the thirteenth year since conception, the current status of this contentious two stage technique is presented and best practices for deployment in the treatment of CRLM is codified.
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http://dx.doi.org/10.1016/j.ijsu.2020.04.009DOI Listing
October 2020

Comparison of the duration of hospital stay after laparoscopic or open distal pancreatectomy: randomized controlled trial.

Br J Surg 2020 09 7;107(10):1281-1288. Epub 2020 Apr 7.

Department of Surgery and Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.

Background: Studies have suggested that laparoscopic distal pancreatectomy (LDP) is advantageous compared with open distal pancreatectomy (ODP) regarding hospital stay, blood loss and recovery. Only one randomized study is available, which showed enhanced functional recovery after LDP compared with ODP.

Methods: Consecutive patients evaluated at a multidisciplinary tumour board and planned for standard distal pancreatectomy were randomized prospectively to LDP or ODP in an unblinded, parallel-group, single-centre superiority trial. The primary outcome was postoperative hospital stay.

Results: Of 105 screened patients, 60 were randomized and 58 (24 women, 41 per cent) were included in the intention-to-treat analysis; there were 29 patients of mean age 68 years in the LDP group and 29 of mean age 63 years in the ODP group. The main indication was cystic pancreatic lesions, followed by neuroendocrine tumours. The median postoperative hospital stay was 5 (i.q.r. 4-5) days in the laparoscopic group versus 6 (5-7) days in the open group (P = 0·002). Functional recovery was attained after a median of 4 (i.q.r. 2-6) versus 6 (4-7) days respectively (P = 0·007), and duration of surgery was 120 min in both groups (P = 0·482). Blood loss was less with laparoscopic surgery: median 50 (i.q.r. 25-150) ml versus 100 (100-300) ml in the open group (P = 0·018). No difference was found in the complication rates (Clavien-Dindo grade III or above: 4 versus 8 patients respectively). The rate of delayed gastric emptying and clinically relevant postoperative pancreatic fistula did not differ between the groups.

Conclusion: LDP is associated with shorter hospital stay than ODP, with shorter time to functional recovery and less bleeding. Registration number: ISRCTN26912858 ( www.isrctn.com).
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http://dx.doi.org/10.1002/bjs.11554DOI Listing
September 2020

Liver resection is beneficial for patients with colorectal liver metastases and extrahepatic disease.

Ann Transl Med 2020 Feb;8(4):109

Department of Surgery and Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.

Background: Liver metastases are the most common cause of death for patients with colorectal cancer and affect up to half of the patients. Liver resection is an established method that can potentially be curative. For patients with extrahepatic disease (EHD), the role of liver surgery is less established.

Methods: This is a retrospective study based on data from the national quality registry SweLiv. Data were obtained between 2009 and 2015. SweLiv is a validated registry and has been in use since 2009, with coverage above 95%. Patients with liver metastases and EHD were analyzed and cross-checked against the national death cause registry for survival analysis.

Results: During the study period, 2,174 patients underwent surgery for colorectal liver metastases (CRLM), and 277 patients with EHD were treated with resection or ablation. The estimated median survival time for the entire cohort from liver resection/ablation was 40 months (95% CI, 32-47). The survival time for patients treated with liver resection was 45 months compared to 26 months for patients treated with ablation (95% CI 38-53, 18-33, P=0.001). A subgroup analysis of resected patients revealed that the group with pulmonary metastases had a significantly longer estimated median survival (50 months; 95% CI, 39-60) than the group with lymph node metastases (32 months; 95% CI, 7-58) or peritoneal carcinomatosis (28 months; 95% CI, 14-41) (P=0.022 and 0.012, respectively). Other negative prognostic factors were major liver resection and nonradical liver resection.

Conclusions: For patients with liver metastases and limited EHD, liver resection results in prolonged survival compared to what can be expected from chemotherapy alone.
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http://dx.doi.org/10.21037/atm.2019.12.125DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7049033PMC
February 2020

Complete Radiologic Response of Metastatic Pancreatic Ductal Adenocarcinoma to Microwave Ablation Combined with Second-Line Palliative Chemotherapy.

Case Rep Gastrointest Med 2020 31;2020:4138215. Epub 2020 Jan 31.

Department of Surgery and Department of Clinical and Experimental Medicine, Linköping University, 58183 Linköping, Sweden.

Pancreatic ductal adenocarcinoma (PDAC) has a bleak prognosis, especially for the majority of patients diagnosed with metastatic disease. The primary option for palliative treatment is chemotherapy, and responses beyond first-line treatment are rare and typically short. Here, we report a case of a 63-year-old woman with PDAC in the head of the pancreas who was initially successfully treated by pancreaticoduodenectomy followed by adjuvant chemotherapy with gemcitabine. However, disease recurrence with liver and para-aortic lymph node metastases was detected only two months after the completion of adjuvant chemotherapy. First-line palliative chemotherapy with gemcitabine-nab/paclitaxel was commenced. The results were discouraging, with disease progression (liver and lung metastases) detected at the first evaluation; the progression-free survival was just two months (64 days). Surprisingly, the response to second-line palliative chemotherapy with 5-fluorouracil-oxaliplatin was excellent; in combination with the ablation of a liver metastasis, this treatment regimen resulted in a complete radiological response and an 11-month treatment-free interval with a sustained good performance status.
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http://dx.doi.org/10.1155/2020/4138215DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7016399PMC
January 2020

ALPPS Improves Survival Compared With TSH in Patients Affected of CRLM: Survival Analysis From the Randomized Controlled Trial LIGRO.

Ann Surg 2021 03;273(3):442-448

Department of Surgery and Clinical and Experimental Medicine, Linköping University, Sweden.

Objective: To evaluate the oncological outcome for patients with colorectal liver metastases (CRLM) randomized to associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) or 2-stage hepatectomy (TSH).

Background: TSH with portal vein occlusion is an established method for patients with CRLM and a low volume of the future liver remnant (FLR). ALPPS is a less established method. The oncological outcome of these methods has not been previously compared in a randomized controlled trial.

Methods: One hundred patients with CRLM and standardized FLR (sFLR) <30% were included and randomized to resection by ALPPS or TSH, with the option of rescue ALPPS in the TSH group, if the criteria for volume increase was not met. The first radiological follow-up was performed approximately 4 weeks postoperatively and then after 4, 8, 12, 18, and 24 months. At all the follow-ups, the remaining/recurrent tumor was noted. After the first follow-up, chemotherapy was administered, if indicated.

Results: The resection rate, according to the intention-to-treat principle, was 92% (44 patients) for patients randomized to ALPPS compared with 80% (39 patients) for patients randomized to TSH (P = 0.091), including rescue ALPPS. At the first postoperative follow-up, 37 patients randomized to ALPPS were assessed as tumor free in the liver, and also 28 patients randomized to TSH (P = 0.028). The estimated median survival for patients randomized to ALPPS was 46 months compared with 26 months for patients randomized to TSH (P = 0.028).

Conclusions: ALPPS seems to improve survival in patients with CRLM and sFLR <30% compared with TSH.
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http://dx.doi.org/10.1097/SLA.0000000000003701DOI Listing
March 2021

Treatment patterns and survival in patients with hepatocellular carcinoma in the Swedish national registry SweLiv.

BJS Open 2020 02 20;4(1):109-117. Epub 2019 Nov 20.

Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.

Background: Consistent data on clinical features, treatment modalities and long-term survival in patients with hepatocellular carcinoma (HCC) using nationwide quality registers are lacking. This study aimed to describe treatment patterns and survival outcomes in patients diagnosed with HCC using a national maintained database.

Methods: Characteristics and treatment patterns in patients diagnosed with HCC and registered in the national register of liver and bile duct tumours (SweLiv) between 2009 and 2016 were reviewed. Overall survival (OS) was estimated using Kaplan-Meier analysis and the log rank test to compare subgroups for clinical features, treatment modalities and outcomes according to the year of treatment.

Results: A total of 3376 patients with HCC were registered over 8 years, 246 (7·3 per cent) of whom underwent transplantation. Some 501 (14·8 per cent) and 390 patients (11·6 per cent) had resection and ablation as primary treatment. Transarterial chemoembolization and systemic sorafenib treatment were intended in 476 (14·1 per cent) and 426 patients (12·6 per cent) respectively; the remaining 1337 (39·6 per cent) were registered but referred for best supportive care (BSC). The 5-year survival rate was approximately 75 per cent in the transplantation group. Median OS was 4·6 (i.q.r. 2·0 to not reached) years after resection and 3·1 (2·3-6·7) years following ablation. In patients referred for palliative treatment, median survival was 1·4 (0·8-2·9), 0·5 (0·3-1·2) and 0·3 (0·1-1·0) years for the TACE, sorafenib and BSC groups respectively (P < 0·001). Median survival was 0·9 years for the total HCC cohort in 2009-2012, before publication of the Swedish national treatment programme, increasing to 1·4 years in 2013-2016 (P < 0·001).

Conclusion: The survival outcomes reported were in line with previous results from smaller cohorts. The introduction of national guidelines may have contributed to improved survival among patients with HCC in Sweden.
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http://dx.doi.org/10.1002/bjs5.50226DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6996573PMC
February 2020

Patient involvement in surgical care-Healthcare personnel views and behaviour regarding patient involvement.

Scand J Caring Sci 2021 Mar 31;35(1):96-103. Epub 2020 Jan 31.

Department of Surgery and Department of Clinical and Experimental Medicine, County Council of Östergötland, Linköping University, Linköping, Sweden.

Background: All professions in surgical care have a responsibility to include patients in their health care. By Swedish law, all care should be done in dialogue with the patient. The essential part of health care is the meeting between patient and healthcare professional. In the interaction, a decision can be made, and needs can be identified to a safer care. Previous studies on patient participation have focussed on patients' perspectives in surgical care, but there is a paucity of studies about the personnel's perspective of estimated patient involvement in surgical care.

Aim: The aim of this study was to identify and describe healthcare personnel's view and behaviour regarding patient involvement in surgical care.

Method: A quantitative study with various professions was conducted. A validated questionnaire was used, remaining questions grouped under following areas: patient involvement, acute phase, hospital time, discharge phase and questions on employment and workplace.

Results: A total of 140 questionnaires were sent out to a surgical clinic in Sweden, and 102 questionnaires were answered. All professionals stated that clear information is an important part of patient involvement in surgical care. Statistically significant differences existed between the professions in the subscale information. Physicians rated their information higher than the Registered Nurses (p = 0.005) and the practical nurses did (p = 0.001). Hindrances to involving patients were lack of time and other priority tasks.

Conclusions: Professionals in surgical care graded information to be the most important thing for patient involvement. Participation in important decisions, including the possibility to express personal views and ask questions, is important factors for patient involvement. Barriers against patient involvement are lack of time and prioritisation of other work activities.
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http://dx.doi.org/10.1111/scs.12823DOI Listing
March 2021

ALPPS for Locally Advanced Intrahepatic Cholangiocarcinoma: Did Aggressive Surgery Lead to the Oncological Benefit? An International Multi-center Study.

Ann Surg Oncol 2020 May 30;27(5):1372-1384. Epub 2020 Jan 30.

Department of General, Visceral and Transplantation Surgery, University Hospital Tuebingen, Tübingen, Germany.

Background: ALPPS is found to increase the resectability of primary and secondary liver malignancy at the advanced stage. The aim of the study was to verify the surgical and oncological outcome of ALPPS for intrahepatic cholangiocarcinoma (ICC).

Methods: The study cohort was based on the ALPPS registry with patients from 31 international centers between August 2009 and January 2018. Propensity score matched patients receiving chemotherapy only were selected from the SEER database as controls for the survival analysis.

Results: One hundred and two patients undergoing ALPPS were recruited, 99 completed the second stage with median inter-stage duration of 11 days. The median kinetic growth rate was 23 ml/day. R0 resection was achieved in 87 (85%). Initially high rates of morbidity and mortality decreased steadily to a 29% severe complication rate and 7% 90-day morbidity in the last 2 years. Post-hepatectomy liver failure remained the main cause of 90-day mortality. Multivariate analysis revealed insufficient future liver remnant at the stage-2 operation (FLR2) to be the only risk factor for severe complications (OR 2.91, p = 0.02). The propensity score matching analysis showed a superior overall survival in the ALPPS group compared to palliative chemotherapy (median overall survival: 26.4 months vs 14 months; 1-, 2-, and 3-year survival rates: 82.4%, 70.5% and 39.6% vs 51.2%, 21.4% and 11.3%, respectively, p < 0.01). The survival benefit, however, was not confirmed in the subgroup analysis for patients with insufficient FLR2 or multifocal ICC.

Conclusion: ALPPS showed high efficacy in achieving R0 resections in locally advanced ICC. To get the most oncological benefit from this aggressive surgery, ALPPS would be restricted to patients with single lesions and sufficient FLR2.
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http://dx.doi.org/10.1245/s10434-019-08192-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7138775PMC
May 2020

Segment 4 occlusion in portal vein embolization increase future liver remnant hypertrophy - A Scandinavian cohort study.

Int J Surg 2020 Mar 28;75:60-65. Epub 2020 Jan 28.

Department of Clinical Science, Intervention and Technology, Division of Surgery, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden. Electronic address:

Background: The additional value of including segment 4 (S4) portal branches in right portal vein embolization (rPVE) is debated. The aim of the study was to explore this in a large multicenter cohort.

Material And Methods: A retrospective cohort study consisting of all patients subjected to rPVE from August 2012 to May 2017 at six Scandinavian university hospitals. PVE technique was essentially the same in all centers, except for the selection of main embolizing agent (particles or glue). All centers used coils or particles to embolize S4 branches. A subgroup analysis was performed after excluding patients with parts of or whole S4 included in the future liver remnant (FLR).

Results: 232 patients were included in the study, of which 36 received embolization of the portal branches to S4 in addition to rPVE. The two groups (rPVE vs rPVE + S4) were similar (gender, age, co-morbidity, diagnosis, neoadjuvant chemotherapy, bilirubin levels prior to PVE and embolizing material), except for diabetes mellitus which was more frequent in the rPVE + S4 group (p = 0.02). Pre-PVE FLR was smaller in the S4 group (333 vs 380 ml, p = 0.01). rPVE + S4 resulted in a greater percentage increase of the FLR size compared to rPVE alone (47 vs 38%, p = 0.02). A subgroup analysis, excluding all patients with S4 included in the FLR, was done. There was no longer a difference in pre-PVE FLR between groups (333 vs 325 ml, p = 0.9), but still a greater percentage increase and also absolute increase of the FLR in the rPVE + S4 group (48 vs 38% and 155 vs 112 ml, p = 0.01 and 0.02).

Conclusion: In this large multicenter cohort study, additional embolization of S4 did demonstrate superior growth of the FLR compared to standard right PVE.
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http://dx.doi.org/10.1016/j.ijsu.2020.01.129DOI Listing
March 2020

Bile spillage should be avoided in elective cholecystectomy.

Hepatobiliary Surg Nutr 2019 Dec;8(6):640-642

Department of Surgery, University Hospital of Linkoping, Linkoping, Sweden.

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http://dx.doi.org/10.21037/hbsn.2019.07.14DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6943005PMC
December 2019

Digital twins to personalize medicine.

Genome Med 2019 12 31;12(1). Epub 2019 Dec 31.

Centre for Personalized Medicine, Linköping University, 581 83, Linköping, Sweden.

Personalized medicine requires the integration and processing of vast amounts of data. Here, we propose a solution to this challenge that is based on constructing Digital Twins. These are high-resolution models of individual patients that are computationally treated with thousands of drugs to find the drug that is optimal for the patient.
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http://dx.doi.org/10.1186/s13073-019-0701-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6938608PMC
December 2019