Publications by authors named "Jozef Urdzik"

14 Publications

  • Page 1 of 1

Case report: An unusual presentation of renal hypertension after damage control surgery.

Int J Surg Case Rep 2021 May 7;82:105872. Epub 2021 Apr 7.

Department of Surgical Sciences, Uppsala University, Sweden.

Introduction And Importance: Hypertensive crisis may be a life-threatening condition to any patient and represents an even more serious condition in trauma patients following severe hemorrhage.

Case Presentation: We present a case were surgical drape packing induced hypertensive crisis in a trauma patient, recently resuscitated from abdominal hemorrhage.

Clinical Discussion: We argue that direct compression of the kidney by the surgical drapes induced hypersecretion of renin with a mechanism equal to Page kidney. The hypertensive crisis as well as the hyperreninemia was resolved after removing the surgical drapes, and the patient's condition returned to normal without any sequelae.

Conclusion: We encourage considering this unusual but important complication when packing of the abdomen has been carried out, and strongly recommend ruling out renin-mediated hypertension as a cause of post-operative hypertension in such cases.
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http://dx.doi.org/10.1016/j.ijscr.2021.105872DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8065272PMC
May 2021

Influence of Proteome Profiles and Intracellular Drug Exposure on Differences in CYP Activity in Donor-Matched Human Liver Microsomes and Hepatocytes.

Mol Pharm 2021 04 19;18(4):1792-1805. Epub 2021 Mar 19.

Department of Pharmacy and Science for Life Laboratory, Uppsala University, 752 37 Uppsala, Sweden.

Human liver microsomes (HLM) and human hepatocytes (HH) are important systems for studies of intrinsic drug clearance (CL) in the liver. However, the CL values are often in disagreement for these two systems. Here, we investigated these differences in a side-by-side comparison of drug metabolism in HLM and HH prepared from 15 matched donors. Protein expression and intracellular unbound drug concentration (Kp) effects on the CL were investigated for five prototypical probe substrates (bupropion-CYP2B6, diclofenac-CYP2C9, omeprazole-CYP2C19, bufuralol-CYP2D6, and midazolam-CYP3A4). The samples were donor-matched to compensate for inter-individual variability but still showed systematic differences in CL. Global proteomics analysis outlined differences in HLM from HH and homogenates of human liver (HL), indicating variable enrichment of ER-localized cytochrome P450 (CYP) enzymes in the HLM preparation. This suggests that the HLM may not equally and accurately capture metabolic capacity for all CYPs. Scaling CL with CYP amounts and Kp could only partly explain the discordance in absolute values of CL for the five substrates. Nevertheless, scaling with CYP amounts improved the agreement in rank order for the majority of the substrates. Other factors, such as contribution of additional enzymes and variability in the proportions of active and inactive CYP enzymes in HLM and HH, may have to be considered to avoid the use of empirical scaling factors for prediction of drug metabolism.
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http://dx.doi.org/10.1021/acs.molpharmaceut.1c00053DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8041379PMC
April 2021

Hepatocyte size fractionation allows dissection of human liver zonation.

J Cell Physiol 2021 Aug 16;236(8):5885-5894. Epub 2021 Jan 16.

Department of Pharmacy, Uppsala University, Uppsala, Sweden.

Human hepatocytes show marked differences in cell size, gene expression, and function throughout the liver lobules, an arrangement termed liver zonation. However, it is not clear if these zonal size differences, and the associated phenotypic differences, are retained in isolated human hepatocytes, the "gold standard" for in vitro studies of human liver function. Here, we therefore explored size differences among isolated human hepatocytes and investigated whether separation by size can be used to study liver zonation in vitro. We used counterflow centrifugal elutriation to separate cells into different size fractions and analyzed them with label-free quantitative proteomics, which revealed an enrichment of 151 and 758 proteins (out of 5163) in small and large hepatocytes, respectively. Further analysis showed that protein abundances in different hepatocyte size fractions recapitulated the in vivo expression patterns of previously described zonal markers and biological processes. We also found that the expression of zone-specific cytochrome P450 enzymes correlated with their metabolic activity in the different fractions. In summary, our results show that differences in hepatocyte size matches zonal expression patterns, and that our size fractionation approach can be used to study zone-specific liver functions in vitro.
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http://dx.doi.org/10.1002/jcp.30273DOI Listing
August 2021

The prognostic value of C-reactive protein and albumin in patients undergoing resection of colorectal liver metastases. A retrospective cohort study.

HPB (Oxford) 2021 Jun 16;23(6):970-978. Epub 2020 Nov 16.

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

Background: The systemic inflammation-based Glasgow Prognostic Score (GPS) and modified GPS (mGPS), as measured by preoperative C-reactive protein (CRP) and albumin, correlate with poor survival in several cancers. This study evaluates the prognostic value of these scores in patients with colorectal liver metastases (CRLM).

Methods: This retrospective study assessed the prognostic role of preoperatively measured GPS and mGPS in patients undergoing liver resection because of CRLM. Clinicopathological data were retrieved from local databases. The prognostic value of GPS and mGPS were compared and a Cox regression model was used to find independent predictors of overall survival.

Results: In total, 849 consecutive patients between January 2005 and December 2015 were included. Patients with GPS 0 had a median survival of 70 months compared to 49 months in patients with GPS 1, and 27 months in patients with GPS 2. Multivariable analyses showed that GPS 1 (HR = 1.51, 95%CI [1.14-2.01]) and GPS 2 (HR = 2.78, 95%CI [1.79-4.31]), after correction for age >70 years (HR = 1.75 [1.36-2.26]), and extended resection (HR = 2.53, 95%CI[1.79-3.58]), were associated with poor overall survival.

Conclusion: A preoperative GPS is an independent prognostic factor in patients with CRLM, and appears to be a better prognostic tool than mGPS.
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http://dx.doi.org/10.1016/j.hpb.2020.10.019DOI Listing
June 2021

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

The Value of CA19-9 After Irreversible Electroporation for Pancreatic Cancer.

Anticancer Res 2019 Nov;39(11):6193-6196

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

Background/aim: Carbohydrate antigen 19-9 (CA19-9) is a tumor marker for pancreatic cancer. Irreversible electroporation (IRE) is an experimental treatment modality for pancreatic cancer. The aim of this study was to evaluate whether percutaneous IRE lowers the CA19-9 level in pancreatic cancer and whether this correlates with improved overall survival.

Patients And Methods: Seventy-one patients with locally advanced pancreatic cancer or local recurrence after resection were treated. Patients with missing data, metastatic disease and normal serum CA19-9 before IRE were excluded. This left 35 cases for analysis.

Results: The median CA19-9 did not decrease in the cohort after IRE treatment (282 U/ml before versus 315 U/ml after; p=0.80). The 25th percentile of patients with the best CA19-9 response had improved overall survival compared to the 25th percentile with the worst response (mean 13.1 versus 8.1 months, respectively; p=0.01).

Conclusion: IRE did not lower the level of CA19-9 in pancreatic cancer cases. However, a response in CA19-9 was correlated with improved survival.
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http://dx.doi.org/10.21873/anticanres.13827DOI Listing
November 2019

ERCP-related perforations: a population-based study of incidence, mortality, and risk factors.

Surg Endosc 2020 05 26;34(5):1939-1947. Epub 2019 Sep 26.

Division of Surgery, CLINTEC, Karolinska Institutet, Center for Digestive Diseases, Karolinska University Hospital, Stockholm, Sweden.

Background: Perforations related to endoscopic retrograde cholangiopancreatography (ERCP) are rare but feared adverse events with highly reported morbidity and mortality rates. The aim was to evaluate the incidence and outcome of ERCP-related perforations and to identify risk factors for death due to perforations in a population-based study.

Methods: Between May 2005 and December 2013, a total of 52,140 ERCPs were registered in GallRiks, a Swedish nationwide, population-based registry. A total of 376 (0.72%) were registered as perforations or extravasation of contrast during ERCP or as perforation in the 30-day follow-up. The patients with perforation were divided into fatal and non-fatal groups and analyzed for mortality risk factors. The case volume of centers and endoscopists were divided into the upper quartile (Q4) and the lower three quartile (Q1-3) groups. Furthermore, fatal group patients' records were reviewed.

Results: Death within 90 days after ERCP-related perforations or at the index hospitalization occurred in 20% (75 out of 376) for all perforations and 0.1% (75 out of 52,140) for all ERCPs. The independent risk factors for death after perforation were malignancy (OR 11.2, 95% CI 5.8-21.6), age over 80 years (OR 3.8, 95% CI 2.0-7.4), and sphincterotomy in the pancreatic duct (OR 2.8, 95% CI 1.1-7.5). In Q4 centers, the mortality was similar with or without pancreatic duct sphincterotomy (14% vs. 13%, p = 1.0), but in Q1-3 centers mortality was higher (45% vs. 21%, p = 0.024).

Conclusions: ERCP-related perforations are severe adverse events with low incidence (0.7%) and high mortality rate up to 20%. Malignancy, age over 80 years, and sphincterotomy in the pancreatic duct increase the risk to die after a perforation. The risk of a fatal outcome in perforations after pancreatic duct sphincterotomy was reduced when occurred at a Q4-center. In the case of a complicated perforation a transfer to a Q4-center may be considered.
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http://dx.doi.org/10.1007/s00464-019-06966-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7113211PMC
May 2020

Percutaneous Irreversible Electroporation as First-line Treatment of Locally Advanced Pancreatic Cancer.

Anticancer Res 2019 May;39(5):2509-2512

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

Background/aim: Irreversible electroporation (IRE) has recently been used as an experimental ablation treatment following systemic chemotherapy in locally advanced pancreatic cancer (LAPC). The primary aim of this study was to evaluate survival of LAPC patients after IRE prior to chemotherapy. The secondary aim was to examine the complication rates.

Patients And Methods: Twenty-four patients with LAPC were included and treated with percutaneous ultrasound-guided IRE under general anesthesia. Survival data from the National Quality Registry for Pancreatic and Periampullary Cancer for LAPC during the same period were used for comparison.

Results: The median survival after diagnosis was 13.3 months in the IRE group compared to 9.9 months in the registry group (p=0.511). Six patients had a severe complication after IRE treatment.

Conclusion: No obvious gain in survival was observed with IRE as the first line treatment of LAPC and IRE was associated with severe complications. This study does not support percutaneous IRE in this setting.
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http://dx.doi.org/10.21873/anticanres.13371DOI Listing
May 2019

A simple approach for restoration of differentiation and function in cryopreserved human hepatocytes.

Arch Toxicol 2019 03 17;93(3):819-829. Epub 2018 Dec 17.

Department of Pharmacy and Science for Life Laboratory, Uppsala University, Uppsala, Sweden.

Primary human hepatocytes are used in all facets of liver research, from in vitro studies of xenobiotic disposition and toxicity to the clinical management of liver failure. Unfortunately, cellular stress during isolation and cryopreservation causes a highly unpredictable loss of the ability to attach and form cell-matrix and cell-cell interactions. Reasoning that this problem could be mitigated at the post-thawing stage, we applied label-free quantitative global proteomics to analyze differences between attached and non-attached fractions of cryopreserved human hepatocyte batches. Hepatocytes that were unable to attach to a collagen matrix showed many signs of cellular stress, including a glycolytic phenotype and activation of the heat shock response, ultimately leading to apoptosis activation. Further analysis of the activated stress pathways revealed an increase in early apoptosis immediately post-thawing, which suggested the possibility of stress reversal. Therefore, we transiently treated the cells with compounds aimed at decreasing cellular stress via different mechanisms. Brief exposure to the pan-caspase apoptosis inhibitor Z-VAD-FMK restored attachment ability and promoted a differentiated morphology, as well as formation of 3D spheroids. Further, Z-VAD-FMK treatment restored metabolic and transport functions, with maintained sensitivity to hepatotoxic insults. Altogether, this study shows that differentiation and function of suboptimal human hepatocytes can be restored after cryopreservation, thus markedly increasing the availability of these precious cells.
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http://dx.doi.org/10.1007/s00204-018-2375-9DOI Listing
March 2019

Global Proteome Changes in Liver Tissue 6 Weeks after FOLFOX Treatment of Colorectal Cancer Liver Metastases.

Proteomes 2016 Oct 14;4(4). Epub 2016 Oct 14.

Department of Surgical Sciences, Uppsala University, SE-75185 Uppsala, Sweden.

(1) Oxaliplatin-based chemotherapy for colorectal cancer liver metastasis is associated with sinusoidal injury of liver parenchyma. The effects of oxaliplatin-induced liver injury on the protein level remain unknown. (2) Protein expression in liver tissue was analyzed-from eight patients treated with FOLFOX (combination of fluorouracil, leucovorin, and oxaliplatin) and seven controls-by label-free liquid chromatography mass spectrometry. Recursive feature elimination-support vector machine and Welch -test were used to identify classifying and relevantly changed proteins, respectively. Resulting proteins were analyzed for associations with gene ontology categories and pathways. (3) A total of 5891 proteins were detected. A set of 184 (3.1%) proteins classified the groups with a 20% error rate, but relevant change was observed only in 55 (0.9%) proteins. The classifying proteins were associated with changes in DNA replication ( < 0.05) through upregulation of the minichromosome maintenance complex and with the innate immune response ( < 0.05). The importance of DNA replication changes was supported by the results of Welch -test ( < 0.05). (4) Six weeks after FOLFOX treatment, less than 1% of identified proteins showed changes in expression associated with DNA replication, cell cycle entry, and innate immune response. We hypothesize that the changes remain after recovery from FOLFOX treatment injury.
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http://dx.doi.org/10.3390/proteomes4040030DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5260963PMC
October 2016

Magnetic resonance imaging flowmetry demonstrates portal vein dilatation subsequent to oxaliplatin therapy in patients with colorectal liver metastasis.

HPB (Oxford) 2013 Apr 20;15(4):265-72. Epub 2012 Aug 20.

Department of Surgery, Uppsala University, 75185 Uppsala, Sweden.

Objectives: Sinusoidal injury (SI) after oxaliplatin-based therapies for colorectal liver metastasis (CRLM) can increase postoperative morbidity. Preoperative methods to estimate SI are lacking. The aim of this study was to identify SI by evaluating portal vein haemodynamics.

Methods: Magnetic resonance imaging flowmetry (MRIF) was used to estimate portal vein haemodynamics in 29 patients with CRLM before liver surgery. Sinusoidal injury was evaluated from resected non-tumorous liver parenchyma according to the combined vascular injury (CVI) score of ≥3.

Results: All patients with SI (six of 29) received oxaliplatin; however, a significant association could not be proven (P= 0.148). Oxaliplatin-treated patients showed portal vein dilatation in both the SI and non-SI groups compared with patients who had not received oxaliplatin (Bonferroni corrected P= 0.003 and P= 0.039, respectively). Mean portal velocity tended to be lower in patients with SI compared with oxaliplatin-treated patients without SI (Bonferroni corrected P= 0.087). A mean portal velocity of ≤14.35 cm/s together with a cross-section area of ≥1.55 cm(2) was found to predict SI with sensitivity of 100% and specificity of 78%.

Conclusions: Oxaliplatin treatment was associated with portal vein dilatation. Patients with SI showed a tendency towards decreased mean portal flow velocity. This may indicate that SI is associated with an increased resistance to blood flow in the liver parenchyma. Portal vein haemodynamic variables estimated by MRIF can identify patients without SI non-invasively.
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http://dx.doi.org/10.1111/j.1477-2574.2012.00540.xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3608980PMC
April 2013

The value of pre-operative magnetic resonance spectroscopy in the assessment of steatohepatitis in patients with colorectal liver metastasis.

J Hepatol 2012 Mar 23;56(3):640-6. Epub 2011 Oct 23.

Department of Surgery, Uppsala University, Uppsala, Sweden.

Background & Aims: Neoadjuvant chemotherapy prior to liver surgery for colorectal metastases can cause marked steatosis (≥ 33%) and steatohepatitis defined by non-alcoholic fatty liver disease activity score (NAS) as adverse effects on liver parenchyma. The aim of this study was to evaluate the steatosis level prior to liver resection using proton magnetic resonance spectroscopy ((1)H MRS) and to compare it with digital quantification of steatosis (DQS) and "classical" histopathology.

Methods: (1)H MRS at 3T evaluated steatosis in 35 patients with colorectal liver metastasis, planned for liver resection. Non-tumorous liver parenchyma samples were obtained after surgery for classical histopathology and DQS utilising automated software for quantification of histopathological slides using image processing.

Results: Classical histopathology defined marked steatosis in nine patients. Histopathology was less reliable than DQS (interclass correlation coefficient - ICC 0.771) or (1)H MRS (ICC 0.722) in steatosis estimation. (1)H MRS showed very similar steatosis levels and high reliability compared to DQS (ICC 0.955). Steatohepatitis was observed in seven patients (NAS ≥ 4) and (1)H MRS was able to predict it with 100% sensitivity and 89% specificity at threshold 10.9%, without knowing lobular inflammation or hepatocyte ballooning. BMI was significantly higher in the groups with marked steatosis and steatohepatitis. Standard blood tests or chemotherapy had no predictive value.

Conclusions: (1)H MRS is a reliable non-invasive tool for steatosis assessment, and interestingly, it was able to predict steatohepatitis defined by NAS ≥ 4 in patients planned for liver resection of colorectal metastases after neoadjuvant chemotherapy.
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http://dx.doi.org/10.1016/j.jhep.2011.10.006DOI Listing
March 2012

Longterm follow-up after transarterial chemotherapy for hepatocellular carcinoma in a Scandinavian centre.

HPB (Oxford) 2010 Nov 2;12(9):637-43. Epub 2010 Sep 2.

Department of Surgery Department of Radiology, Uppsala University, Uppsala, Sweden.

Background: Transarterial chemotherapy infusion (TAI) with lipiodol is a palliative treatment for hepatocellular carcinoma. The aim of this study was to describe the outcomes of TAI from a single scandinavian centre between 1995 to 2008.

Methods: The study is a retrospective analyse of prospectively collected data. TAI (doxorubicin, 50 mg with lipiodol) was administrated every 6 weeks. After 5 treatments, a CT scan was performed, and if the disease was stable, (RECIST score) treatment was continued.

Results: 57 patients with HCC were treated with TAI. Median age; 72 years (52-84), 41 (71%) men. 52 (91%) had Child-Pugh score A, and 5 (9%) had Child-Pugh B. Nine (16%) patients had a BCLC score A, 19 (33%) B, 29 (51%) C, while none was classified as BCLC D. Twenty nine (51%) patients had a tumour size ≥ 10 cm. In total 254 treatments were performed, a median of 4 (1-20) per patient. Treatment mortality was 0%. In 30 (53%) patients the treatment strategy was not completed due to deteriorating clinical conditions. Median survival was 17 months (2-108), 2, 3, and 5-years survival was 34%, 22%, and 13%, respectively. Patients that responded to treatment (n = 23) had a median survival of 26 (13-108) months compared to 8 (2-48) months for those not fulfilling the treatment plan, p < 0.05. Tumour size ≥ 10 cm, AFP ≥ 400 µg/l, and Child-Pugh class B or C were negative prognostic factors for survival, p < 0.05.

Conclusions: The 5 year survival was 13%, and median survival 17 months. Treatment mortality was 0%. Patients that responded to treatment (40%) had a median survival of 26 months. TAI provides good palliation but selection of patients is crucial.
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http://dx.doi.org/10.1111/j.1477-2574.2010.00210.xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2999791PMC
November 2010

Right hemihepatectomy.

J Gastrointest Surg 2008 Jul 16;12(7):1283-7. Epub 2008 Feb 16.

Department of Surgery, Uppsala University Hospital, Uppsala SE-751 85, Sweden.

A right hemihepatectomy is frequently required for surgical removal of colorectal liver metastases. Today, this procedure can be performed quite safely provided the remaining liver is free from significant disease including steatohepatitis due to prolonged cytostatic treatment. Standard surgical techniques for liver resection are described in surgical textbooks. However, each center has developed its own modifications of important details. In this paper, we describe our technique to resect the right liver lobe using conventional surgical techniques as well as a vascular stapler and an ultrasonic dissector. This technique has proven to be quite safe, and blood loss is most often not significant despite we do not routinely apply the Pringle's manoeuvre during the division of the liver parenchyma.
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http://dx.doi.org/10.1007/s11605-008-0493-zDOI Listing
July 2008
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