Publications by authors named "Saulius Paskauskas"

16 Publications

  • Page 1 of 1

Performance of the IOTA ADNEX Model on Selected Group of Patients with Borderline Ovarian Tumours.

Medicina (Kaunas) 2020 Dec 11;56(12). Epub 2020 Dec 11.

Department of Obstetrics and Gynaecology, Medical Academy, Lithuanian University of Health Sciences, LT-44307 Kaunas, Lithuania.

ultrasound is considered to be the primary tool for preoperative assessment of ovarian masses; however, the discrimination of borderline ovarian tumours (BOTs) is challenging, and depends highly on the experience of the sonographer. The Assessment of Different NEoplasias in the adneXa (ADNEX) model is considered to be a valuable diagnostic tool for preoperative assessment of ovarian masses; however, its performance for BOTs has not been widely studied, due to the low prevalence of these tumours. The aim of this study was to evaluate the performance of ADNEX model for preoperative diagnosis of BOTs. retrospective analysis of preoperative ultrasound datasets of patients diagnosed with BOTs on the final histology after performed surgery was done at a tertiary oncogynaecology centre during the period of 2012-2018. 85 patients were included in the study. The performance of ADNEX model based on absolute risk (AR) improved with the selection of a more inclusive cut-off value, varying from 47 (60.3%) correctly classified cases of BOTs, with the selected cut-off of 20%, up to 67 (85.9%) correctly classified cases of BOTs with the cut-off value of 3%. When relative risk (RR) was used to classify the tumours, 59 (75.6%) cases were identified correctly. Forty (70.2%) cases of serous and 16 (72.7%) cases of mucinous BOTs were identified when AR with a 10% cut-off value was applied, compared to 44 (77.2%) and 15 (68.2%) cases of serous and mucinous BOTs, correctly classified by RR. The addition of Ca125 improved the performance of ADNEX model for all BOTs in general, and for different subtypes of BOTs. However, the differences were insignificant. The International Ovarian Tumour Analysis (IOTA) ADNEX model performs well in discriminating BOTs from other ovarian tumours irrespective of the subtype. The calculation based on RR or AR with the cut-off value of at least 10% should be used when evaluating for BOTs.
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http://dx.doi.org/10.3390/medicina56120690DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7763161PMC
December 2020

Transcutaneous Electric Nerve Stimulation Reduces Acute Postoperative Pain and Analgesic Use After Open Inguinal Hernia Surgery: A Randomized, Double-Blind, Placebo-Controlled Trial.

J Pain 2021 05 10;22(5):533-544. Epub 2020 Dec 10.

Department of General Surgery, Lithuanian University of Health Sciences, Kaunas, Lithuania.

In this randomized, double-blind, placebo-controlled trial, we evaluated the role of transcutaneous electrical nerve stimulation (TENS) in the multimodal treatment (nonopioid analgesics and kinesiotherapy) of postoperative pain following open inguinal hernia repair. In total, 80 males participants with elective primary unilateral hernia Lichtenstein repair were randomly allocated to receive TENS or a placebo-TENS procedure. The TENS group received local and segmental conventional TENS on the first and second postoperative days. In the placebo-TENS group, intensity was set at 0 to 0.5mA. Change of pain level at rest, when walking, when standing up from bed, pressure algometry parameters and additional analgesic use were the main outcomes. Reduction of VAS pain score and absolute and relative pain relief were observed in the TENS group following the procedures compared to the placebo-TENS group (P< .001). The pressure pain threshold and maximal tolerable pressure in the hernia side were equal before the TENS procedure in both groups (P= .84), but after the procedure, these were higher in TENS group (P< .001). Additional nonopioid analgesics requirements were lower in the TENS group on the first and second postoperative days (P< .001). TENS is a safe procedure that can reduce postoperative pain and analgesic use after open inguinal hernia repair. The study was registered in the database of clinicaltrials.gov (register number NCT03739060). PERSPECTIVE: This article presents TENS as a safe and effective nonpharmacologic intervention to reduce postoperative pain after open inguinal hernia repair. TENS could be used in daily practice as part of a multimodal postoperative pain treatment, especially for patients suffering from hyperalgesia.
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http://dx.doi.org/10.1016/j.jpain.2020.11.006DOI Listing
May 2021

Stimulated upregulation of is associated with inadequate response of gastric and ovarian cancer cell lines to hyperthermia and cisplatin treatment.

Oncol Lett 2019 Aug 18;18(2):1961-1968. Epub 2019 Jun 18.

Institute for Digestive Research, Lithuanian University of Health Sciences, LT-50161 Kaunas, Lithuania.

Heme oxygenase (HO)-1 is a heat shock protein induced by hyperthermia, responsible for cellular resistance to temperature. The aim of this study was to clarify the response of gastric and ovarian cancer cells to hyperthermic intraperitoneal chemotherapy, following the modulation of expression. AGS and OVCAR-3 cells were treated with different temperature regimens, either alone or in combination with an IC dose of cisplatin for 1 h. Prior to treatment, expression was silenced by short interfering RNA transfection. In OVCAR-3 cells, cisplatin increased mRNA expression by 3.73-fold under normothermia and 2.4-fold under hyperthermia; furthermore, these factors similarly increased protein expression levels. Exposure to cisplatin under hyperthermia reduced the viability of OVCAR-3 cells by 36% and -silencing enhanced this effect by 20%. -silencing under normothermia increased apoptotic rates in cisplatin-treated OVCAR-3 cells by 2.07-fold, and hyperthermia enhanced the effect by 3.09-fold. Semi-quantitative polymerase chain reaction (PCR) cell analysis indicated that exposure to cisplatin decreased the cell index under normothermia, and that hyperthermia boosted this effect in OVCAR-3. In AGS cells, only temperature increased cellular levels. Silencing in AGS cells at 37°C reduced viability by 16% and increased apoptotic rates 2.63-fold. Hyperthermia did not affect AGS viability; however, apoptosis was increased 6.84-fold. PCR analysis indicated no additional effects of hyperthermia on the AGS cell index. is induced in cancer cells by different stressors in a variable manner. In tumors with highly inducible , prior silencing of this gene could improve the cellular response to hyperthermia and cisplatin.
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http://dx.doi.org/10.3892/ol.2019.10489DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6607092PMC
August 2019

Hyperthermia potentiates cisplatin cytotoxicity and negative effects on mitochondrial functions in OVCAR-3 cells.

J Bioenerg Biomembr 2019 08 22;51(4):301-310. Epub 2019 Jul 22.

Department of Obstetrics and Gynaecology Lithuanian University of Health Sciences, Eiveniu str.2, LT-50009, Kaunas, Lithuania.

The aim of this study was to determine the effects of hyperthermia, cisplatin and their combination on mitochondrial functions such as glutamate dehydrogenase (GDH) activity and mitochondrial respiration rates, as well as survival of cultured ovarian adenocarcinoma OVCAR-3 cells. Cells treated for 1 h with hyperthermia (40 and 43 °C) or cisplatin (IC50) or a combination of both treatments were left for recovery at 37 °C temperature for 24 h or 48 h. The obtained results revealed that 43 °C hyperthermia potentiated effects of cisplatin treatment: combinatory treatment more strongly suppressed GDH activity and expression, mitochondrial functions, and decreased survival of OVCAR-3 cells in comparison to separate single treatments. We obtained evidence that in the OVCAR-3 cell line GDH was directly activated by hyperthermia (cisplatin eliminated this effect); however, this effect was followed by GDH inhibition after 48 h recovery. A combination of 43 °C hyperthermia with cisplatin induced stronger GDH inhibition in comparison to separate treatments, and negative effects exerted on GDH activity correlated with suppression of mitochondrial respiration with glutamate + malate. Cisplatin did not induce uncoupling of oxidative phosphorylation in OVCAR-3 cells but induced impairment of the outer mitochondrial membrane in combination with 43 °C hyperthermia. Hyperthermia (43 °C) potentiated cytotoxicity of cisplatin in an OVCAR-3 cell line.
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http://dx.doi.org/10.1007/s10863-019-09805-8DOI Listing
August 2019

Associations among Serum Lipocalin-2 Concentration, Human Papilloma Virus and Clinical Stage of Cervical Cancer.

Medicina (Kaunas) 2019 May 30;55(6). Epub 2019 May 30.

Department of Obstetrics and Gynaecology, Medical Academy, Lithuanian University of Health Sciences, LT 44307 Kaunas, Lithuania.

Lipocalin 2 (LCN2) has an oncogenic role in promoting tumorigenesis through enhancing tumor cell proliferation and the metastatic potential. The aim of our study was to determine whether serum LCN2 could serve as a diagnostic marker of cervical cancer (CC) and to evaluate the correlation between its serum concentration, the clinical stage of the cancer and Human Papilloma Virus HPV infections in women. A total of 33 women with histologically proven cervical cancer (CC), 9 women with high- grade cervical intraepithelial neoplasia (HSIL) and 48 healthy women (NILM) were involved in the study. A concentration of LCN2 was assayed with the Magnetic LuminexR Assay multiplex kit. An HPV genotyping kit was used for the detection and differentiation of 15 high-risk (HR) HPV types in the liquid-based cytology medium (LBCM) and the tissue biopsy. The majority (84.8%) of the women were infected by HPV16 in the CC group, and there was no woman with HPV16 in the control group ( < 0.01). Several types of HR HPV were found more often in the LBCM compared to in the tissue biopsy ( = 0.044). HPV16 was more frequently detected in the tissue biopsy than the LBCM ( < 0.05). The LCN2 level was higher in HPV-positive than in HPV-negative women ( = 0.029). The LCN2 concentration was significantly higher in women with stage IV than those with stage I CC ( = 0.021). Conclusions: Many HR HPV types, together with HPV16/18, can colonize the vagina and cervix, but often HPV16 alone penetrates into the tissue and causes CC. The serum LCN2 concentration was found to be associated not only with HR HPV infection, irrespective of the degree of cervical intraepithelial changes, but also with advanced clinical CC stage. LCN2 could be used to identify patients with advanced disease, who require a more aggressive treatment.
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http://dx.doi.org/10.3390/medicina55060229DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6630730PMC
May 2019

Narrow line between benefit and harm: Additivity of hyperthermia to cisplatin cytotoxicity in different gastrointestinal cancer cells.

World J Gastroenterol 2018 Mar;24(10):1072-1083

Institute for Digestive Research, Lithuanian University of Health Sciences, Kaunas LT-50161, Lithuania.

Aim: To investigate the response to hyperthermia and chemotherapy, analyzing apoptosis, cytotoxicity, and cisplatin concentration in different digestive system cancer cells.

Methods: AGS (gastric cancer cell line), Caco-2 (colon cancer cell line) and T3M4 (pancreatic cancer cell line) were treated by cisplatin and different temperature setting (37 °C to 45 °C) either in isolation, or in combination. Treatment lasted for one hour. 48 h after the treatment viability was evaluated by MTT, cell apoptosis by Annexin V-PE and 7ADD flow cytometry. Intracellular cisplatin concentration was measured immediately after the treatment, using mass spectrometry. Isobologram analysis was performed to evaluate the mathematical combined effect of temperature and cisplatin.

Results: AGS cells were the most sensitive to isolated application of hyperthermia. Hyperthermia, in addition to cisplatin treatment, did not provoke a synergistic effect at intervals from 37 °C to 41 °C in neither cancer cell line. However, a temperature of 43 °C enhanced cisplatin cytotoxicity for Caco-2 cells. Moreover, isobologram analysis revealed mathematical antagonistic effects of cisplatin and temperature combined treatment in AGS cells; variations between synergistic, additive, and antagonistic effects in Caco-2 cells; and additive and antagonistic effects in T3M4 cells. Combined treatment enhanced initiation of cell apoptosis in AGS, Caco-2, and T3M4 cells by 61%, 20%, and 19% respectively. The increase of intracellular cisplatin concentration was observed at 43 °C by 30%, 20%, and 18% in AGS, Caco-2, and T3M4 cells, respectively.

Conclusion: In addition to cisplatin, hyperthermia up to 43 °C does not affect the viability of cancer cells in a synergistic manner.
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http://dx.doi.org/10.3748/wjg.v24.i10.1072DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5850127PMC
March 2018

Response of OVCAR-3 Cells to Cisplatin and Hyperthermia: Does Hyperthermia Really Matter?

Anticancer Res 2017 09;37(9):5011-5018

Institute for Digestive Research, Lithuanian University of Health Sciences, Kaunas, Lithuania.

Background: Hyperthermic intraperitoneal chemotherapy (HIPEC) is proposed as a promising treatment method, but fundamental information about the contribution of hyperthermia to intraperitoneal chemotherapy is lacking. The purpose of this study was to investigate the cytotoxic effect of hyperthermia and cisplatin on OVCAR-3 cells in vitro.

Materials And Methods: Imitating the typical clinical conditions of HIPEC, OVCAR-3 cells were exposed to hyperthermia and cisplatin for 1 h. MTT viability test, flow cytometric analysis, and real-time cell and isobologram analysis were performed.

Results: Hyperthermia up to 42°C did not significantly increase the effect of cisplatin regarding the viability and apoptosis of OVCAR-3 cells. Moreover, an antagonistic effect of hyperthermia and cisplatin was revealed.

Conclusion: Our investigation of OVCAR-3 cells critically disputes the benefit of hyperthermia in ovarian cancer treatment. Further in vitro and in vivo research is essential for better understanding of the mechanisms of action of hyperthermia and its role in the treatment of epithelial ovarian cancer.
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http://dx.doi.org/10.21873/anticanres.11915DOI Listing
September 2017

Upregulation of cugbp2 increases response of pancreatic cancer cells to chemotherapy.

Langenbecks Arch Surg 2016 Feb 21;401(1):99-111. Epub 2015 Dec 21.

Institute for Digestive System Research, Lithuanian University of Health Sciences, Eiveniu str. 4, Kaunas, 50161, Lithuania.

Purpose: Altered expression and/or function of ribosomal RNA (rRNA)-binding proteins CUGBP2/CELF2 might influence post-transcriptional regulation of the HO-1- and COX-2-mediated cytoprotective pathways and represents an important therapeutic target. The aim of this study was to assess the effects of CUGBP2-mediated post-transcriptional regulation of COX-2 and HO-1 in pancreatic cancer cells in regard of response to gemcitabine (GEM) treatment.

Methods: Expression of CUGBP2, COX-2, and HO-1 was evaluated using qRT-PCR and Western blot methods. Cell viability after treatment with GEM and/or curcumin and siCUGBP2 was evaluated using MTT and crystal violet tests. RNA immunoprecipitation analysis was used to confirm COX-2 and HO-1 post-transcriptional regulation by CUGBP2 protein.

Results: CUGBP2 expression at the messenger RNA (mRNA) level was 2.2-fold lower (p = 0.007), but HO-1 and COX-2 expression was increased 6.9- (p = 0.023) and 2.3- (p = 0.046) fold in pancreatic cancer tissues. The median survival of patients with low CUGBP2 expression from the lowest tercile was 13.8 months. The median survival of patients in terciles of middle and high CUGBP2 expression levels was 21.9 month (p = 0.123). Induction of CUGBP2 expression by curcumin resulted in the downregulation of HO-1 and COX-2 and strongly sensitized tumor cells to GEM treatment. However, CUGBP2 silencing upregulated HO-1 and COX-2 protein expression and had a high effect on cells viability.

Conclusion: Decreased activity of CUGBP2 could be associated with high chemoresistance and early dissemination of pancreatic cancer through the HO-1- and COX-2-mediated cytoprotective and carcinogenesis pathways. Curcumin significantly increased the effectiveness of GEM treatment in vitro via the CUGBP2-mediated post-transcriptional regulation pathway.
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http://dx.doi.org/10.1007/s00423-015-1364-1DOI Listing
February 2016

Referral pattern, management, and long-term results of laparoscopic bile duct injuries: a case series of 44 patients.

Medicina (Kaunas) 2012 ;48(3):138-44

Department of Surgery, Medical Academy, Lithuanian University of Health Sciences, Eivenių 2, 50028 Kaunas, Lithuania.

Background And Objective: The incidence of bile duct injuries (BDIs) after laparoscopic cholecystectomy (LC) is higher than after open cholecystectomy, and the management of these lesions is still controversial. This study analyzed diagnostic and management strategies as well as long-term outcomes after BDI.

Material And Methods: A prospective database of patients with BDIs at the Clinic of Surgery was maintained during the 8-year period (2000-2007). The long-term results were evaluated during 2008-2010, after 36- to 120-month follow-up (median, 84 months).

Results: In our series, 21 patients (48%) presented with minor and 23 (52%) with major BDIs. The overall incidence of BDIs was 0.24%. In 92% of cases in the minor BDI group, endoscopic stenting resulted in a good outcome. Major BDIs were treated by immediate, early, or delayed surgery depending on the timeliness of diagnosis and presence of biliary sepsis and/or cholangitis. The mean estimated time to failure after the initial treatment in the minor BDI group was significantly longer when compared with the major BDI group (114.3 vs. 81.8 months, log-rank test P=0.048). The hazard ratio of initial treatment failure after major versus minor BDIs was 6.06 (95% CI, 1.01-17.59). The mean estimated time to develop a biliary stricture after immediate, early, and delayed reconstructions was not different (P>0.05 in pairwise comparisons by log-rank test).

Conclusions: Minor BDIs are best served by endoscopy, while surgical repair may be an efficient option when injury is diagnosed intraoperatively. The timing of reconstruction after major BDIs does not portend a different outcome; consequently, every attempt to achieve infection control should be warranted. Referral to a tertiary care center should be encouraged to facilitate a proper classification of preoperative injuries and multidisciplinary approach.
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September 2012

Blockade of leukocyte haptokinesis and haptotaxis by ketoprofen, diclofenac and SC-560.

BMC Immunol 2011 Nov 12;12:64. Epub 2011 Nov 12.

Department of Surgery, University of Heidelberg, Germany.

Background: Nonsteroidal anti-inflammatory drugs (NSAID) represent a one of the most widely used anti-inflammatory substances. Their anti-inflammatory effects are mainly based on inhibition of cyclooxygenase. The potential direct effect of NSAID on leukocyte migration was poorly investigated. Using time-lapse microscopy and 96-well fluorescence-based assay, we studied the effect of three different NSAID, ketoprofen, diclofenac and SC-560, on leukocyte haptokinesis and haptotaxis in vivo and in vitro.

Results: NSAID induced an immediate inhibiting effect on leukocyte migration both in vitro and in vivo. This effect was dose-dependent and was not restricted to a specific type of leukocytes. The inhibition of leukocyte migration by NSAID was partially re-stored after removal of inhibiting agent. Only complete blockade of leukocyte migration was accompanied by a strong reduction of [Ca(2+)]i.

Conclusions: NSAID strongly supress leukocyte migration. The results of the present study may have important clinical implications since blockade of leukocyte migration can be achieved after topical application of NSAID.
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http://dx.doi.org/10.1186/1471-2172-12-64DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3247092PMC
November 2011

Colonic intussusception caused by colonic lipoma: a case report.

Medicina (Kaunas) 2010 ;46(7):477-81

Department of Surgery, Kaunas University of Medicine, and Department of General Surgery, Kaunas 2nd Clinical Hospital, Eivenių 2, 50028 Kaunas, Lithuania.

Intussusception is a pediatric condition that rarely presents in adults. Colonic lipomas 4 cm and more in diameter can cause colonic intussusception leading to emergency operation. Surgical resection of the involved segment must be the procedure of choice. We report a case of colonic intussusception caused by colonic lipoma in an adult. The patient underwent operation, and histopathological examination of the specimen confirmed the diagnosis of colonic submucosal lipoma.
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December 2010

Facial skin metastasis of colorectal cancer: a case report.

Cases J 2010 Jan 15;3:28. Epub 2010 Jan 15.

Departments of Surgery, Kaunas University of Medicine, Kaunas, Eiveniu 2, 50009 Kaunas, Lithuania.

Introduction: Liver and lungs are common locations of distant metastases of colorectal cancer. Skin metastases of colorectal cancer are very rare, and facial lesions are extremely uncommon.

Case Presentation: An anterior resection of the rectum was performed for rectal cancer T3N0M0G3. A small ulcer on the upper lip developed 3.5 years after primary operation. Metastasis of adenocarcinoma was confirmed histologically, and local excision was performed. At the same time, a solitary metastasis in the right lung was diagnosed, and the right lower lobectomy was performed. No other metastasis or local recurrences were observed during the next 7 months.

Conclusion: Skin metastases in the face from colorectal cancer are very rare and may indicate tumour relapse several years after primary resection. These patients have a worse prognosis.
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http://dx.doi.org/10.1186/1757-1626-3-28DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2821305PMC
January 2010

Percutaneous transhepatic biliary stenting: the first experience and results of the Hospital of Kaunas University of Medicine.

Medicina (Kaunas) 2008 ;44(12):969-76

Department of Surgery, Kaunas University of Medicine, Eiveniu 2, 50009 Kaunas, Lithuania.

Malignant biliary obstruction may be caused by cholangiocarcinoma and other nonbiliary carcinomas. At the time of diagnosis, 90% of patients with malignant obstructive jaundice may benefit from palliative treatment only. The objective of palliation is to relieve jaundice-related symptoms, prevent cholangitis, prolong survival, and improve quality of life. Percutaneous transhepatic biliary stenting is a well-established procedure used in patients with malignant obstruction of intra- and extrahepatic bile ducts. Twelve patients (9 women, 3 men; mean age, 68 years; range, 44-88 years) with inoperable malignant biliary obstruction were selected for percutaneous transhepatic biliary stenting with metallic stents in the period from January to December 2007. Technical and clinical success rate in this patient series was 83% and 80%, respectively. Minor and major complications occurred in 17% and 8% of cases, respectively, which is in the range reported by the others. This is our first experience of percutaneous transhepatic biliary stenting at the Hospital of Kaunas University of Medicine and, to our knowledge, the first reported patient series in Lithuania. These first results encourage expanding effective palliation by the employment of the percutaneous transhepatic biliary stenting in patients with nonresectable malignant biliary obstruction or in case of a recurrent disease after curative surgery. The cost effectiveness of percutaneous transhepatic biliary stenting against percutaneous transhepatic biliary drainage has yet to be evaluated in a prospective manner. However, immediate clinical benefits and positive short-term outcomes are unequivocal.
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February 2009

The role of estrogen in the formation of experimental abdominal aortic aneurysm.

Am J Surg 2009 Jan 30;197(1):49-54. Epub 2008 Jun 30.

Third General Surgery Department, Affiliated ZhongShan Hospital, DaLian University, DaLian 116001, China.

Objective: The current study sought to investigate the role of estrogen in the formation of experimental abdominal aortic aneurysm (AAA).

Methods: Elastase perfusion of infrarenal AAA animal model was performed in 20 female and 20 male Wistar rats that were randomly divided into an ovariectomized/sham-operated group and an estradiol (E2) experimental/saline control group, respectively. At day 14, E2 was detected, while the mRNA and protein expressions of matrix metalloproteinases 2 and 9 (MMP-2 and -9) in AAA tissue were detected by immunohistochemistry and polymerase chain reaction (PCR).

Results: The ovariectomized group showed lower estrogen levels and a higher aneurysm dilatation rate and significantly higher MMP-2 and -9 expression compared with the sham-operated group (P < .01), which was in accordance with MMP-2 and -9 mRNA expression. The E2 group showed higher estrogen levels and a lower aneurysm dilatation rate and significantly lower MMP-2 and -9 expression than did the saline control group (P < .01), which was in accordance with MMP-2 and -9 mRNA expression.

Conclusions: In the pathogenesis of AAA, estrogen may play an inhibitory role by decreasing expression of MMP-2 and MMP-9 synthesis.
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http://dx.doi.org/10.1016/j.amjsurg.2007.11.022DOI Listing
January 2009

Venous thromboembolism and prophylaxis in cancer patients.

Medicina (Kaunas) 2008 ;44(3):175-81

Department of Surgery, Kaunas University of Medicine, Eiveniu 2, 50009 Kaunas, Lithuania.

Venous thromboembolism is a serious complication in patients with cancer. The seriousness of venous thromboembolism as a complication in cancer patients is becoming recognized as an important medical issue. Venous thromboembolism is a multifactorial disease associated with vascular endothelial damage, stasis of blood flow, and hypercoagulation. Preexisting morbidity, mutations of factor V Leiden or prothrombin 20210A, type of cancer, presence of metastases, use of central venous access, surgery, anesthesia, etc., increase the risk of venous thromboembolism. The patients with malignancies have a 7-fold increase in the risk of venous thromboembolism compared with individuals without cancer. Venous thromboembolism is the second most common cause of mortality in cancer patients. Venous thromboembolism is the most common cause of death at 30 days after surgery in patients undergoing surgery for cancer. Venous thromboembolism caused death in 46.3% of the cases after surgery for cancer. The Geneva prognostic index identified predictive factors for an adverse outcome, and the American College of Chest Physicians (ACCP) has suggested the guidelines for the prevention of venous tromboembolism in cancer patients. Cancer patients should receive appropriate venous thromboembolism prophylaxis. The methods used for venous thromboembolism prophylaxis are mechanical, pharmacological, or a combination of both. Well-timed thromboprophylaxis may protect patients from venous thromboembolism, early lethal outcome and even influence survival.
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May 2008

Active leukocyte crawling in microvessels assessed by digital time-lapse intravital microscopy.

J Surg Res 2006 Oct 21;135(2):291-6. Epub 2006 Apr 21.

Department of Surgery, University of Heidelberg, Heidelberg, Germany.

Objective: The ability of active movement is an important feature of leukocytes. Here, we used a hybrid technique that combines intravital microscopy and digital time-lapse video microscopy to investigate the physiology and molecular mechanisms of intravascular leukocyte movement.

Methods: Intravital microscopy of mesenteric venules was performed in male, Wistar rats using digital video recording and time-lapse image compression. The leukocyte movement and extravasation were analyzed after local application of TNF-alpha, after blockade of endothelial (anti-ICAM-1 antibody) and leukocyte (anti-CD18 antibody) adhesion molecules. Additionally, the migratory activity of isolated leukocytes in collagen gel was analyzed and compared with their intravascular locomotion.

Results: Adherent leukocytes showed an active intraluminal crawling along the endothelial lining. Most permanent stickers (84 +/- 13%) crawled actively on the intraluminal site of venules. Baseline measurement of leukocyte crawling velocity yielded an average 9.0 +/- 1.8 mum/min that was not significantly different from crawling velocity of extravascular leukocytes (8.9 +/- 4.5 mum/min). The maximum distance of leukocyte crawling observed was 150 microm. The maximum time of crawling was 15 min. Intraluminal crawlers traveled over a mean distance of 35 +/- 17 mum with the average duration of 5.4 +/- 1.4 min. Under unstimulated conditions, almost all crawling leukocytes detached from the endothelium and did not migrate through the vascular wall. TNF-alpha induced a significant increase of leukocyte extravasation. Anti-ICAM-1 and anti-CD18 antibodies significantly reduced leukocyte crawling. The proportion of isolated migrating leukocytes in collagen gel (87% +/- 6%) was not significantly different from the percentage of intravascular crawling leukocytes in vivo.

Conclusions: The method of digital time-lapse intravital microscopy represents an advantageous technology for the investigation of intravascular, transendothelial, and extravascular migration of leukocytes. Using this technology, we showed that leukocyte-endothelial-interactions are an active and dynamic process. This process involves long-time (several minutes) crawling of leukocytes along the endothelium and, finally, detachment from the endothelium. Intravascular leukocyte crawling reflects the migratory potential of circulating leukocytes and strongly depends on the expression of adhesion molecules. For extravasation, an additional pro-inflammatory stimulus is required.
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http://dx.doi.org/10.1016/j.jss.2006.02.020DOI Listing
October 2006
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