Publications by authors named "Ioannis Petridis"

28 Publications

  • Page 1 of 1

Performance of the model for end-stage liver disease score for mortality prediction and the potential role of etiology.

J Hepatol 2021 Jul 30. Epub 2021 Jul 30.

Gastroenterology Unit, ASL Latina, Department of Translational and Precision Medicine, "Sapienza" University of Rome, Italy.

Background & Aims: Although the discriminative ability of the model for end-stage liver disease (MELD) score is generally considered acceptable, its calibration is still unclear. In a validation study, we assessed the discriminative performance and calibration of 3 versions of the model: original MELD-TIPS, used to predict survival after transjugular intrahepatic portosystemic shunt (TIPS); classic MELD-Mayo; and MELD-UNOS, used by the United Network for Organ Sharing (UNOS). We also explored recalibrating and updating the model.

Methods: In total, 776 patients who underwent elective TIPS (TIPS cohort) and 445 unselected patients (non-TIPS cohort) were included. Three, 6 and 12-month mortality predictions were calculated by the 3 MELD versions: discrimination was assessed by c-statistics and calibration by comparing deciles of predicted and observed risks. Cox and Fine and Grey models were used for recalibration and prognostic analyses.

Results: In the TIPS/non-TIPS cohorts, the etiology of liver disease was viral in 402/188, alcoholic in 185/130, and non-alcoholic steatohepatitis in 65/33; mean follow-up±SD was 25±9/19±21 months; and the number of deaths at 3-6-12 months was 57-102-142/31-47-99, respectively. C-statistics ranged from 0.66 to 0.72 in TIPS and 0.66 to 0.76 in non-TIPS cohorts across prediction times and scores. A post hoc analysis revealed worse c-statistics in non-viral cirrhosis with more pronounced and significant worsening in the non-TIPS cohort. Calibration was acceptable with MELD-TIPS but largely unsatisfactory with MELD-Mayo and -UNOS whose performance improved much after recalibration. A prognostic analysis showed that age, albumin, and TIPS indication might be used to update the MELD.

Conclusions: In this validation study, the performance of the MELD score was largely unsatisfactory, particularly in non-viral cirrhosis. MELD recalibration and candidate variables for an update to the MELD score are proposed.

Lay Summary: While the discriminative performance of the model for end-stage liver disease (MELD) score is credited to be fair to good, its calibration, the correspondence of observed to predicted mortality, is still unsettled. We found that application of 3 different versions of the MELD in 2 independent cirrhosis cohorts yielded largely imprecise mortality predictions particularly in non-viral cirrhosis. Thus, we propose a recalibration and suggest candidate variables for an update to the model.
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http://dx.doi.org/10.1016/j.jhep.2021.07.018DOI Listing
July 2021

Hypofractionated FLASH-RT as an Effective Treatment against Glioblastoma that Reduces Neurocognitive Side Effects in Mice.

Clin Cancer Res 2021 02 15;27(3):775-784. Epub 2020 Oct 15.

Laboratory of Radiation Oncology/DO/Radio-Oncology/CHUV, Lausanne University Hospital and University of Lausanne, Switzerland.

Purpose: Recent data have shown that single-fraction irradiation delivered to the whole brain in less than tenths of a second using FLASH radiotherapy (FLASH-RT), does not elicit neurocognitive deficits in mice. This observation has important clinical implications for the management of invasive and treatment-resistant brain tumors that involves relatively large irradiation volumes with high cytotoxic doses.

Experimental Design: Therefore, we aimed at simultaneously investigating the antitumor efficacy and neuroprotective benefits of FLASH-RT 1-month after exposure, using a well-characterized murine orthotopic glioblastoma model. As fractionated regimens of radiotherapy are the standard of care for glioblastoma treatment, we incorporated dose fractionation to simultaneously validate the neuroprotective effects and optimized tumor treatments with FLASH-RT.

Results: The capability of FLASH-RT to minimize the induction of radiation-induced brain toxicities has been attributed to the reduction of reactive oxygen species, casting some concern that this might translate to a possible loss of antitumor efficacy. Our study shows that FLASH and CONV-RT are isoefficient in delaying glioblastoma growth for all tested regimens. Furthermore, only FLASH-RT was found to significantly spare radiation-induced cognitive deficits in learning and memory in tumor-bearing animals after the delivery of large neurotoxic single dose or hypofractionated regimens.

Conclusions: The present results show that FLASH-RT delivered with hypofractionated regimens is able to spare the normal brain from radiation-induced toxicities without compromising tumor cure. This exciting capability provides an initial framework for future clinical applications of FLASH-RT..
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http://dx.doi.org/10.1158/1078-0432.CCR-20-0894DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7854480PMC
February 2021

Adult to Adult Living Donor Liver Transplantation in Recipients with Low MELD: A Strategy Intended to Overcome Donor Shortage.

Dig Dis Sci 2020 12;65(12):3477-3480

Department for the Treatment and Study of Abdominal Diseases and Abdominal Transplantation, IRCCS (Istituto di Ricovero e Cura a Carattere Scientifico) "ISMETT (Istituto Mediterraneo per i Trapianti e Terapie ad Alta Specializzazione)- UPMC (University of Pittsburgh Medical Center) Italy", Via E. Tricomi 5, 90127, Palermo, Italy.

Recent series have demonstrated advantages of living donor over deceased donor liver transplantation, with particular benefit for those with low model for end-stage liver disease score. The logic underlying the transplantation of patients before they become too sick is intuitive. It reduces mortality and drop outs from the waiting list and makes transplant surgery less demanding. Those principles have to be balanced with donor safety and transplant benefit for the recipient avoiding early, futile transplantation. The authors report a case of adult to adult right lobe living donor liver transplantation performed for a recipient affected by primary biliary cirrhosis with MELD score of 15, in a transplant center located in an area of Europe characterized by chronic organ shortage.
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http://dx.doi.org/10.1007/s10620-020-06522-wDOI Listing
December 2020

Impact of Extended-Criteria Donor Liver Grafts on Benchmark Metrics of Clinical Outcome After Liver Transplantation: A Single Center Experience.

Transplant Proc 2020 Jun 26;52(5):1588-1592. Epub 2020 Mar 26.

Department for the Treatment and Study of Abdominal Diseases and Abdominal Transplantation, IRCCS-ISMETT (Istituto di Ricovero e Cura a Carattere Scientifico - Istituto Mediterraneo per i Trapianti e Terapie ad alta specializzazione), UPMC (University of Pittsburgh Medical Center) Italy, Palermo, Italy; Department of Surgery and Surgical and Medical Specialties, University of Catania, Catania, Italy. Electronic address:

Background: The adoption of extended criteria for donors remains the best strategy to widen the pool of available liver graft against the chronic shortage of donors. Benchmarking in liver transplantation (LT) offers the unprecedented opportunity to compare clinical outcome measures to a set of validated reference values. We aimed to evaluate the impact of marginal grafts usage in a cohort of low-risk benchmark cases from an area with a very low rate of deceased donation.

Methods: A cohort of low-risk benchmark cases was identified from all adult patients who underwent LT at our center. Among these patients, those transplanted with a graft from an extended-criteria donor (ECD) were identified. Benchmark metrics (length of hospital and intensive care unit stay, incidences of mortality, graft loss, and postoperative complication) were compared with benchmark cutoffs and between the 2 groups.

Results: Two hundred forty-five patients satisfied the inclusion criteria, 146 (60%) of whom received an organ from an ECD. Overall, all benchmark metrics where within the cutoffs limits, except for graft loss (14% vs 11%) and mortality (10% vs 9% 1 year after LT). The ECD group was associated with more grade III complications (60% vs 45%, P = .031), graft loss (18% vs 8%, P = .038), and mortality (14% vs 4%, P = .009). Hepatocellular carcinoma diagnosis was found to be associated with less mortality (odds ratio = 0.42, P = .048).

Conclusion: While ECD graft usage is associated with slightly worse prognosis, our experience suggests that their use can be considered safe, especially when matched on hepatocellular carcinoma recipients.
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http://dx.doi.org/10.1016/j.transproceed.2020.02.050DOI Listing
June 2020

Radiation exposure during transjugular intrahepatic portosystemic shunt creation in patients with complete portal vein thrombosis or portal cavernoma.

Radiol Med 2020 Jul 18;125(7):609-617. Epub 2020 Feb 18.

Radiology Service, Department of Diagnostic and Therapeutic Services, Mediterranean Institute for Transplantation and Advanced Specialized Therapies (IRCCS-ISMETT), Via Ernesto Tricomi, 5, 90127, Palermo, PA, Italy.

Background: This study aims to evaluate radiation exposure in patients with complete portal vein thrombosis (CPVT) or portal cavernoma (PC) undergoing transjugular intrahepatic portosystemic shunt (TIPS) creation using real-time ultrasound guidance for portal vein targeting.

Materials And Methods: This is a single institution retrospective analysis. Between August 2009 and September 2018, TIPS was attempted in 49 patients with CPVT or PC. Radiation exposure (dose area product [DAP], air KERMA (AK) and fluoroscopy time [FT]), technical success, clinical success, complications and survival were analyzed.

Results: In total, 29 patients had CPVT and 20 patients had PC. 41/49 patients had cirrhosis. TIPS indications were refractory ascites (n =  25), variceal bleeding (n = 16) and other (n = 8). TIPS was successfully placed in 94% (46/49) of patients via a transjugular approach alone (n = 40), a transjugular/transhepatic approach (n = 5) and a transjugular/transsplenic approach (n = 1). Median DAP was 261 Gy * cm (range 29-950), median AK was 0.2 Gy (range 0.05-0.5), and median FT was 28.2 min (range 7.7-93.7). Mean portosystemic pressure gradient decreased from 16.8  ±  5.1 mmHg to 7.5  ±  3.3 mmHg (P <  0.01). There were no major procedural complications. Overall clinical success was achieved in 77% of patients (mean follow-up of 21.1 months). Encephalopathy was observed in 16 patients (34%), grade II-III encephalopathy in 7 patients (15%). TIPS revision was performed in 15 patients (32%). Overall survival rate was 75%.

Conclusion: In our experience, the use of real-time ultrasound guidance allowed the majority of the TIPS to be performed via a transjugular approach alone with a reasonably low radiation exposure considering the high technical difficulties of the selected cohort of patients with CVPT or PC.
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http://dx.doi.org/10.1007/s11547-020-01155-5DOI Listing
July 2020

Guillain-Barré syndrome after orthotopic liver transplantation: A clinical manifestation of immune reconstitution inflammatory syndrome?

Clin Neurol Neurosurg 2018 10 10;173:140-143. Epub 2018 Aug 10.

Abdominal Surgery and Organ Transplantation Unit, Department for the Treatment and Study of Abdominal Diseases and Abdominal Transplantation, Mediterranean Institute for Transplantation and Advanced Specialized Therapies (IRCCS-ISMETT), Via Ernesto Tricomi 5, 90127, Palermo, Italy.

Guillain-Barrè Syndrome, as part of the spectrum of dysimmune neuropathies, is unexpected to occur in immunocompromised hosts. We describe a clinical case of Guillain-Barrè syndrome, occurred a few weeks after a liver transplant, and we postulate that our case would satisfy all requirements to explain this peripheral nervous system complication as a clinical manifestation of an Immune reconstitution inflammatory syndrome. In this setting of liver transplantation, complicated by potentially multiple infective triggers, reduction of immunosuppression and reversal of pathogen-induced immunosuppression, through antimicrobial therapy, may have led to pro-inflammatory response. The pro-inflammatory pattern would have sustained the pathophysiologic mechanism of this immune neuropathy.
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http://dx.doi.org/10.1016/j.clineuro.2018.07.021DOI Listing
October 2018

Transjugular Intrahepatic Portosystemic Shunt Using the New Gore Viatorr Controlled Expansion Endoprosthesis: Prospective, Single-Center, Preliminary Experience.

Cardiovasc Intervent Radiol 2019 Jan 2;42(1):78-86. Epub 2018 Aug 2.

Radiology Service, Department of Diagnostic and Therapeutic Services, Mediterranean Institute for Transplantation and Advanced Specialized Therapies (IRCCS-ISMETT), Via Ernesto Tricomi 5, 90127, Palermo, Italy.

Objectives: To evaluate short-term clinical efficacy, complications and possible passive stent expansion of transjugular intrahepatic portosystemic shunt (TIPS) creation using the new controlled expansion ePTFE covered stent (VCX), for portal hypertension complications.

Methods: Between 7/2016 and 3/2018, 75 patients received TIPS using VCX. Thirty-nine patients with VCX dilated with an 8-mm angioplasty balloon underwent computed tomography (CT) study during follow-up and CT data were used to measure stent diameter. The CT measurement technique was validated by ex vivo experiment.

Results: TIPS indications were: refractory ascites (n = 45), variceal bleeding (n = 22), other (n = 8). Mean follow-up was 5.8 months (± 4.5, range 1-20). In 69 patients, TIPS was dilated to 8 mm of diameter reaching the hemodynamic target of a portosystemic pressure gradient (PSG) < 12 mmHg. In six patients, not reaching the hemodynamic target the stent was dilated to 10 mm of diameter during the same session with a final PSG < 12 mmHg. Overall clinical success was achieved in 66/75 (88%) patients (80% in refractory ascites, 95% variceal bleeding, 100% other). Grade II-III encephalopathy was observed in five patients (6%). TIPS revision with stent dilatation to 10 mm was performed in seven patients: in three patients with ascites persistence, without evidence of stent dysfunction and in four patients for stent stenosis. One patient underwent stent reduction. Fourteen patients (18%) died during follow-up of causes not related to TIPS. Five patients (6%) underwent liver transplant. No passive stent expansion was detected by CT measurements.

Conclusion: VCX for TIPS creation retains its diameter over a short-term period and is associated with a good clinical outcome with a reasonably low complication rate.
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http://dx.doi.org/10.1007/s00270-018-2040-yDOI Listing
January 2019

Transjugular Intrahepatic Portosystemic Shunts in Patients with Cirrhosis with Refractory Ascites: Comparison of Clinical Outcomes by Using 8- and 10-mm PTFE-covered Stents.

Radiology 2017 07 25;284(1):281-288. Epub 2017 Jan 25.

From the Department of Diagnostic and Therapeutic Services (R.M., L.M., M.D., A.L.), Research Office (F.T.), and Hepatology Unit (I.P.), IRCCS-ISMETT (Mediterranean Institute for Transplantation and Advanced Specialized Therapies), Via Tricomi 5, 90127 Palermo, Italy.

Purpose To compare the efficacy and complications of transjugular intrahepatic portosystemic shunt (TIPS) creation performed by using a 10-mm or an 8-mm-diameter polytetrafluoroethylene (PTFE)-covered stent in a consecutive series of patients with cirrhosis with refractory ascites (RA). Materials and Methods The institutional review board approved this retrospective study and informed consent was waived. One hundred seventy-one patients with RA (mean age, 58.7 years ± 10.3; 95% confidence interval [CI]: 57.2 years, 60.3 years) had undergone TIPS placement by using 10-mm (60 patients) or 8-mm (111 patients) covered stent between January 2004 and December 2012. Median follow-up time was 16.8 months (range, 3.4-84.8 months). Hemodynamic changes, incidence of hepatic encephalopathy, and long-term (>3 months) need for paracentesis after TIPS placement were evaluated and calculated by using the Kaplan-Meier method and were compared by using the log-rank test. Results Pre-TIPS demographics and clinical characteristics of the two groups were comparable. The portosystemic gradient before TIPS was 17.0 mm Hg ± 4.2 (95% CI: 15.9 mm Hg, 18.1 mm Hg) in the 10-mm group versus 16.1 mm Hg ± 3.7 (95% CI: 15.4 mm Hg, 16.8 mm Hg) in the 8-mm group (P = .164). After TIPS, the portosystemic gradient was 6.5 mm Hg ± 3.4 (95% CI: 5.7 mm Hg, 7.4 mm Hg) in the 10-mm group versus 7.5 mm Hg ± 2.6 (95% CI: 6.9 mm Hg, 7.9 mm Hg) in the 8-mm group (P = .039). The long-term need for paracentesis was greater in the 8-mm group (64 of 111 patients [58%] vs 18 of 60 patients [31%], P = .003). Overall, hepatic encephalopathy was similar in both groups (45 of 111 patients [41%] vs 26 of 60 patients [44%], P = .728). Conclusion A10-mm PTFE-covered stent leads to better control of RA secondary to portal hypertension in patients with cirrhosis, compared with an 8-mm stent, without increasing the incidence of hepatic encephalopathy. RSNA, 2017.
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http://dx.doi.org/10.1148/radiol.2017161644DOI Listing
July 2017

Complications and Near-Miss Events After Hepatectomy for Living-Related Liver Donation: An Italian Single Center Report of One Hundred Cases.

Ann Transplant 2016 Sep 22;21:596-601. Epub 2016 Sep 22.

Department for the Treatment and Study of Abdominal Diseases and Abdominal Transplantation, Abdominal Surgery and Organ Transplantation Unit, Istituto Mediterraneo per i Trapianti e Terapie ad Alta Specializzazione (IRCCS-ISMETT), Palermo, Italy.

BACKGROUND In healthy individuals, such as liver living donors, potential complications may occur during surgery. Reporting such complications and near-miss events is mandatory to improve living donor management and safety. MATERIAL AND METHODS This retrospective study was performed on a prospective database with the aim of providing a brief analysis of the perioperative, medium-term, and long-term complications, and the near-miss events in a single center series of 100 consecutive liver resections for adult-to-adult living-donor liver transplantation. RESULTS Only 23.3% of potential living donors underwent surgery. No living donor mortality was reported; 29 patients (29%) experienced at least one complication. Five patients developed mild long-term dysfunction; two aborted hepatectomies, and there were two near-miss events reported. CONCLUSIONS A strategy for an accurate assessment of living donor complications and strict selection criterion cannot be overemphasized, as well as the need to continuously update center patient outcome reports.
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http://dx.doi.org/10.12659/aot.899662DOI Listing
September 2016

Ultrasonographic findings in the ovine udder during lactogenesis in healthy ewes or ewes with pregnancy toxaemia.

J Dairy Res 2015 Aug 1;82(3):293-303. Epub 2015 Jul 1.

Veterinary Faculty,University of Thessaly,43100 Karditsa,Greece.

Objective of the study was to record, by means of ultrasonographic examination, changes occurring during lactogenesis in the udder of healthy ewes and of ewes with pregnancy toxaemia. The work was carried out in 28 ewes, 16 with pregnancy toxaemia (group A) and 12 healthy controls (group B). B-mode and Doppler ultrasonographic examination of the udder of ewes was performed. During the last month of pregnancy, grey-scale intensity values of mammary parenchyma in group A were significantly greater than in group B (P = 0.007), as was also the progressive increase in grey-scale intensity values in both groups (P < 0.001). Blood mammary input was significantly greater in ewes of group B than in ewes of group A (P < 0.05), as was also the progressive increase in blood input in both groups (P < 0.001). Further, differences between the two groups were identified in pulsatility index (P = 0.007) and in mean blood velocity (P = 0.036), but only during the last fortnight of pregnancy. After lambing, grey-scale values decreased sharply compared to those in pregnancy (P < 0.01), whilst blood input, pulsatility index and mean blood velocity continued the same trend as at the last stage of pregnancy, with differences between the two groups still prevalent (P < 0.05). There was a reverse correlation between grey-scale intensity values and milk quantities (P < 0.035) and a correlation between blood input and milk quantities (P < 0.07). The progressive increase in the diameter of the external pudendal artery was significant (P < 0.001), but no significant differences were evident between the two groups (P > 0.35). Differences between group A and group B in all other haemodynamic parameters studied were not significant, neither throughout the last month of pregnancy (P > 0.25), nor during the first week of lactation (P > 0.06). However, their progressive changes during the last month of pregnancy were significant (P < 0.02).
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http://dx.doi.org/10.1017/S0022029915000382DOI Listing
August 2015

Liver Transplantation for Hemoperitoneum Secondary to Huge Multiple Hemangiomatosis: A Case Report of a Tele-intensive Care Unit in Deceased-Donor Management.

Telemed J E Health 2015 Jun 25;21(6):499-502. Epub 2015 Feb 25.

3Hepatology Units, Department for the Treatment and Study of Abdominal Diseases and Abdominal Transplantation, Mediterranean Institute for Transplantation and Advanced Specialized Therapies, Palermo, Italy.

Background: Patients with growing and nonresectable liver hemangiomas should be followed up by a transplant center with extensive experience in complex liver disease. They could be treated on an emergency basis with orthotopic liver transplantation, with an expectation of good long-term results.

Materials And Methods: We describe the case of a 37-year-old woman with liver hemangiomatosis followed up for 8 years, who presented with bleeding requiring transfusions and developed hemodynamic instability. We listed her for emergency transplant before her sister's living donor work-up could be completed. A liver from a cadaveric donor became available at a small local hospital with no experience in organ donation. Tele-intensive care unit (tele-ICU) technology was used for providing clinical data electronically to physicians, nurses, and other critical care specialists, creating medication orders, and communicating with on-site caregivers to implement changes in donor care.

Results: The recipient was transplanted on an emergency basis with a specific customization and application of the telemedicine system in the management of the organ procurement by the recipient team. Tele-ICU technology was used for providing an effective intensive care unit service, managing and stabilizing the deceased donor and allowing the procurement to be carried out uneventfully.

Conclusions: Tele-ICU technology could be a promising resource for emergency transplantation, reducing the urgent need for a living donation and allowing prompt recipient team management of the deceased donor. Our first tele-ICU case offers early confirmation of the feasibility of the telemedicine system in deceased-donor management.
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http://dx.doi.org/10.1089/tmj.2014.0145DOI Listing
June 2015

Ultrasonographic findings in the ovine udder during involution.

J Dairy Res 2014 Aug 4;81(3):288-96. Epub 2014 Jun 4.

Veterinary Faculty,University of Thessaly,43100 Karditsa,Greece.

The objective of the study was to record, by means of ultrasonographic examination, changes occurring in the udder of ewes during involution and to compare differences between progressive or abrupt udder drying-off. In group A ewes, udder drying-off took place progressively during a period of 22 d; ewes were milked twice daily for the last time on day(D) 0; then, they were hand-milked once daily for a week (D1-D7), which was followed by another week during which ewes were hand-milked once every 2 d (D9, D11, D13), followed by a third week during which ewes were hand-milked once every 3 d (D16, D19, D22). In group B ewes, the procedure took place abruptly; ewes were milked twice daily for the last time on D0 and no milking was carried out after that. B-mode and Doppler ultrasonographic examination of the udder of all ewes was performed throughout the drying-off procedure. Appropriate data management and analysis were performed. Progressive changes of the various parameters evaluated throughout the study period were significant in both groups (P<0.005). Gray-scale results of mammary parenchyma progressively decreased during the study and differed significantly between group A and group B (P=0.049). A temporary increase in cistern volume was evident after cessation of lactation, but differences were not significant between the two groups (P>0.3). Diameter of the external pudendal artery progressively decreased during the study and differed significantly between the two groups (P=0.037). Both resistance index and pulsatility index progressively increased throughout the study period in both groups; for both parameters, differences between the two groups were significant (P<0.0005). B-mode ultrasonographic examination indicated differences in remodelling of the extracellular matrix in relation to the procedure for udder drying-off. Volume of the gland cistern did not appear to be affected by the procedure for udder drying-off. Doppler ultrasonographic examination confirmed that blood flow during initiated involution was lower than during a progressive procedure for drying-off.
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http://dx.doi.org/10.1017/S0022029914000223DOI Listing
August 2014

Administration of antibiotics to ewes at the beginning of the dry-period.

J Dairy Res 2014 Feb 9;81(1):9-15. Epub 2013 Oct 9.

Veterinary Faculty, University of Thessaly, 43100 Karditsa, Greece.

The objective of the present paper is to review the significance of administration of antibiotics at the end of a lactation period/beginning of the dry-period in ewes. During the stage of active involution, there is an increased risk of new mastitis cases and recrudescence of subclinical infections that had occurred during the previous lactation period. The main pathogens involved in the so-called 'dry-period mastitis' are coagulase-negative staphylococci. The principle of antibiotic administration at the end of a lactation period involves the intramammary infusion of a preparation to both mammary glands of ewes in the flock. Although a variety of products is licensed for administration in ewes, preferably the product for administration should be selected on the results of susceptibility testing of bacteria to be isolated from samples from ewes in the flock. In many clinical studies from around the world, performed in dairy- or mutton-production flocks, administration of antimicrobial agents at the end of a lactation period has been found beneficial in curing intramammary infections present at cessation of a lactation period, as well as in minimising the risk for intramammary infections during the dry-period. In dairy flocks, there are also benefits from increase in milk yield and decrease flock bulk milk mean somatic cell counts during the subsequent lactation period. Antibiotic administration at drying-off may be performed to all animals in a flock ('complete') or only to those considered to be infected ('selective'). In all cases, after administration of the antibiotic, definite and complete cessation of the lactation period is essential for success of the procedure. Moreover, maintenance of the prescribed withdrawal periods is essential to safeguard public health. The procedure should always be applied as part of a strategic udder health management plan in a flock; implementation improves the welfare of animals and affords significant financial benefits to the farmer. A mastitis prevention scheme during lactation will minimise the incidence of the disease; effective treatment of cases of the disease during lactation will decrease the bacterial populations in the flock and limit risk of infection of other animals. Administration of antibiotics at the end of a lactation period will complement the above procedures and will contribute to improved mammary health for the forthcoming lactation period.
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http://dx.doi.org/10.1017/S0022029913000472DOI Listing
February 2014

Association of KCNJ11 E23K gene polymorphism with hypoglycemia in sulfonylurea-treated type 2 diabetic patients.

Diabetes Res Clin Pract 2012 Oct 14;98(1):119-24. Epub 2012 May 14.

Laboratory of Pharmacology, Medical School, Democritus University of Thrace, Greece.

Aims: In addition to sulfonylurea-induced severe hypoglycemia, which however is not common in T2DM patients treated solely with oral hypoglycemic drugs, mild hypoglycemia is a frequent adverse event affecting many patients treated with oral hypoglycemic drugs and has a serious impact in patient adherence to therapy and everyday clinical practice. The aim of the present study was to investigate the possible association of KCNJ11 E23K polymorphism with incidence of sulfonylurea-induced mild hypoglycemic events.

Methods: 176 T2DM patients receiving sulfonylurea were included in the study, including 92 that had experienced drug-associated hypoglycemia and 84 that had never experienced hypoglycemia while on sulfonylurea treatment. KCNJ11 E23K polymorphism was detected by use of PCR-RFLP method.

Results: Frequencies of KCNJ11 E23K genotypes and alleles were not different between hypoglycemic and non-hypoglycemic T2DM patients (p=0.35 and p=0.47, respectively). In logistic regression analysis before and after adjustment for other factors known to affect this condition (age, body mass index, sulfonylurea mean daily dose, duration of T2DM, renal function and CYP2C9 genotype) KCNJ11 E23K polymorphism did not affect hypoglycemia risk.

Conclusions: KCNJ11 E23K polymorphism is not associated with increased risk of mild hypoglycemia in sulfonylurea-treated T2DM patients.
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http://dx.doi.org/10.1016/j.diabres.2012.04.017DOI Listing
October 2012

Changing picture of central nervous system complications in liver transplant recipients.

Liver Transpl 2011 Nov;17(11):1279-85

Mediterranean Institute for Transplantation and High Specialization Therapies, University of Pittsburgh Medical Center in Italy, Palermo, Italy.

Central nervous system (CNS) complications are common after liver transplantation (LT). According to the literature, the most common causes are infections and the neurotoxicity of immunosuppressive drugs (cyclosporine and tacrolimus). The aim of this study was to evaluate the incidence, clinical presentations, etiologies, and outcomes of CNS complications in a series of 395 consecutive LT recipients whose immunosuppression regimen was designed for low tacrolimus blood levels. An analysis of the 12-hour trough concentrations of tacrolimus in the study population showed that the target drug levels, which were designed to maintain minimal immunosuppression, were usually achieved. In all, 64 patients (16.2%) developed major neurological symptoms (37 within 30 days of LT). None of the observed CNS complications were caused by infections (viral, bacterial, or fungal), and only 3 of the 395 patients (0.8%) received a diagnosis of tacrolimus-related leukoencephalopathy. Cerebrovascular disease was identified in 15 patients (3.8%; 8 had cerebral hemorrhages, 5 had ischemic strokes, and 2 had subdural hemorrhages). Pontine myelinolysis was found in 2 patients (0.5%). Notably, no clear cause was identified for the remaining 44 cases (11.1%): brain imaging was negative for 22 cases, and diffuse hypoxic changes were present for the other 22. CNS complications were significantly associated with a reduction in 3-month patient survival (88.8% versus 95.4%) and 5-year patient survival (57.3% versus 84.1%). Among the pretransplant variables that were analyzed, the incidence of portosystemic encephalopathy, the peak serum bilirubin levels, and the lowest serum total cholesterol levels were significantly different between the 64-patient group with CNS complications and the asymptomatic group of 331 patients.
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http://dx.doi.org/10.1002/lt.22383DOI Listing
November 2011

Association of VKORC1 -1639 G>A polymorphism with carotid intima-media thickness in type 2 diabetes mellitus.

Diabetes Res Clin Pract 2011 Nov 20;94(2):236-41. Epub 2011 Jul 20.

Lab of Pharmacology, Medical School, Democritus University of Thrace, Dragana Campus, 68100 Alexandroupolis, Greece.

Aims: Media calcification is a predictor of cardiovascular mortality in type 2 diabetes mellitus (T2DM). Undercarboxylation of some vitamin K-dependent proteins, due to genetic polymorphisms of VKORC1, can lead to calcification. We examined a potential association between VKORC1 -1639 G>A polymorphism and T2DM and, also, the association of this polymorphism with carotid intima-media thickness (cIMT).

Methods: VKORC1 -1639 G>A polymorphism was determined in 299 T2DM patients and 328 controls of Caucasian origin using PCR-RFLP. cIMT was measured in a subgroup of 118 T2DM patients.

Results: The frequency of VKORC1 genotypes between diabetic and nondiabetic subjects differed significantly (p=0.01). VKORC1 genotype was associated with T2DM in an adjusted model (OR 1.36, p=0.009). A statistically significant difference was observed in the maximum value of cIMT among different genotypes. VKORC1 -1639 G>A polymorphism was an independent predictor of cIMT (p=0.029) after adjusting for established risk factors.

Conclusions: The association between VKORC1 -1639 G>A polymorphism and risk of T2DM could be due to the higher prevalence of calcification in T2DM patients. This is supported by the independent association between VKORC1 -1639 G>A polymorphism and maximum cIMT in T2DM patients which is likely due to atherosclerosis characterized by increased calcification.
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http://dx.doi.org/10.1016/j.diabres.2011.06.021DOI Listing
November 2011

Mass spectrometry measurement of plasma hepcidin for the prediction of iron overload.

Clin Chem Lab Med 2011 Feb 14;49(2):197-206. Epub 2010 Dec 14.

Department of Surgical and Gastroenterological Sciences, University of Padova, Padova, Italy.

Background: Hepcidin has emerged as the primary regulator of iron homeostasis. Previous studies on assessing urinary hepcidin are limited. We developed a method for quantifying hepcidin-25 (Hep-25) in plasma using surface-enhanced laser-desorption-ionization time-of-flight mass spectrometry (SELDI-TOF/MS) and a 25-AA peptide as reference standard. The aims of the study were 1) to assess the performance of this method in different conditions of iron metabolism disorders; 2) to assess the diagnostic validity of non-invasive serum biomarkers in the identification of iron overload.

Methods: Validation of the method was performed in 10 patients with type I hemochromatosis (HE) and in 177 subjects previously enrolled in a general population epidemiological study. Among the latter group, 17 had non-alcoholic fatty liver disease, 10 had chronic hepatitis C, and 150 subjects had normal ultrasound, normal liver function tests (LFTs), an alcohol intake < 20 g ethanol/day and were negative for the C282Y mutation. The following biomarkers were assayed in each case: plasma Hep-25, C282Y and H63D mutations of the HFE gene; serum iron, ferritin (SF), transferrin saturation, transaminases, γ-glutamyltransferase (GGT), glucose, insulin, total cholesterol, high-density lipoprotein (HDL)-cholesterol, low-density lipoprotein (LDL)-cholesterol and triglycerides.

Results: Plasma Hep-25 concentrations were higher in HCV+ patients (26.3 ± 7.2 nmol/L) than in controls, and correlated positively with SF (p < 0.001). H63D heterozygous subjects revealed a pattern of iron overload that was significantly higher than H63D wild type subjects. Analyzing the data with the Biomarker Pattern 5.0.2. software to identify the most significant biomarkers for discriminating between HE cases and controls allowed us to produce an algorithm with four terminal nodes, which included glucose > 4.8 mmol/L and Hep-25/SF ratio ≤ 6.6 as the main splitters. These variables enabled the correct diagnosis of HE with 100% sensitivity, 93% specificity and an area under the receiver operating characteristic (ROC) curve of 0.993.

Conclusions: Our plasma Hep-25 mass spectrometry method yields measurements that reflect pathological and genetic influences; simple non-invasive biomarkers (Hep-25/SF ratio and glucose) can predict the presence of HE.
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http://dx.doi.org/10.1515/CCLM.2011.055DOI Listing
February 2011

Lamivudine monoprophylaxis for de novo HBV infection in HBsAg-negative recipients with HBcAb-positive liver grafts.

Clin Transplant 2011 Jan-Feb;25(1):E77-81. Epub 2010 Oct 11.

Istituto Mediterraneo Trapianti e Terapie ad Alta Specializzazione, Palermo, Italy.

We followed the efficacy of long-term lamivudine monotherapy in preventing development of de novo hepatitis B (DNHB) in a large cohort of hepatitis B surface antigen (HBsAg)-negative recipients with grafts from hepatitis B core antibody (HBcAb)-positive donors. Recipients were observed over a long follow-up. Between July 1999 and December 2008, 45 patients (median age 54, range 19-67) who were HBsAg negative before transplantation were included in the study of monoprophylaxis with lamivudine starting on post-operative day 1, and continuing for life. Mean follow-up: 37.9 months; median 32.1 months (range 2.4-117). No suspension of therapy was reported during the study. Post-transplantation, no DNHB was observed in follow-up: all 45 HBsAg-negative recipients remained HBsAg and HBV DNA negative. Thirty-four of these HBsAg-negative recipients were alive at conclusion of the study. A total of 11 patients died, five of HCV recurrence, two of hepatocellular carcinoma (HCC) recurrence, two of disseminated KSV infection, and two of multiorgan failure because of early graft dysfunction. Patient and graft survival of HBsAg-negative recipients with HBcAb-positive donor grafts (45 cases) were not significantly different from those of the HBsAg-negative recipients with HBcAb-negative donor grafts (302 cases). In our experience, lamivudine monoprophylaxis provided complete protection against HBV reactivation and showed long-term efficacy.
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http://dx.doi.org/10.1111/j.1399-0012.2010.01329.xDOI Listing
June 2011

Transjugular intrahepatic portosystemic shunt with accidental diagnosis of persistence of the left superior vena cava.

World J Gastroenterol 2010 Mar;16(9):1158-60

Department of Gastroenterology and Hepatology, Mediterranean Institute for Transplantation and Advanced Specialized Therapies, University of Pittsburgh Medical Center, Via Tricomi 1, Palermo 90127, Italy.

Transjugular intrahepatic portosystemic shunt (TIPSS) is considered a valid therapeutic option for the treatment of portal hypertension and its complications. The guidelines for this procedure have already been established on the basis of the normal vascular anatomy and of various technical radiological aspects. In some few rare cases, diagnosis of a congenital vascular anomaly can be made accidentally by interventional radiologists, making the procedure of the TIPSS placement extremely difficult or in some cases technically impossible. This report describes a rare vascular malformation characterized by the absence of the right superior vena cava and persistence of the left superior vena cava in a patient with a diagnosis of advanced liver cirrhosis who needed a TIPSS placement in order to control refractory ascites.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2835796PMC
http://dx.doi.org/10.3748/wjg.v16.i9.1158DOI Listing
March 2010

Association of polymorphisms of the serotonergic system with smoking initiation in Caucasians.

Drug Alcohol Depend 2010 Apr 8;108(1-2):70-6. Epub 2010 Jan 8.

Laboratory of Pharmacology, Medical School, Democritus University of Thrace, Dragana Campus, Alexandroupolis 68100, Greece.

Background: The serotonergic system may be implicated in susceptibility to nicotine dependence as nicotine increases 5-hydroxytryptamine (5-HT) release in brain and symptoms of nicotine withdrawal may be modulated by diminished serotonergic neurotransmission. We examined the association of polymorphisms of genes involved in release and receptor function of 5-HT with cigarette smoking initiation in subjects of Caucasian origin.

Methods: 5-HTTLPR polymorphism of the 5-HT transporter gene and -759C/T (rs3813929) and -697G/C (rs518147) polymorphisms of the 5-HT(2C) receptor gene were analyzed in 172 smoking initiators and 254 non-initiators, using PCR-RFLP method. Smoking behavior was assessed with a questionnaire about tobacco use.

Results: We found no differences in the frequency of the 5-HTTLPR genotypes between smoking initiators and non-initiators. However, the frequency of 5-HT(2C) -759T allele was significantly higher in non-initiators than smoking initiators (29.5% vs 16.3%, p=0.002) and the same was true for 5-HT(2C) -697C allele carriers (48.8% vs 34.9%, p=0.004). Sex-dependent analysis revealed that these increased frequencies of -759T and -697C allele carriers were present only in males. No association was observed between any quantitative measures of smoking and these three polymorphisms.

Conclusions: 5-HTTLPR polymorphism was not associated with smoking initiation in either male or female subjects. However, significant association was found between 5-HT(2C) receptor gene polymorphisms and smoking initiation in male Caucasian subjects.
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http://dx.doi.org/10.1016/j.drugalcdep.2009.11.015DOI Listing
April 2010

The serotonin transporter promoter polymorphism (5-HTTLPR) is associated with type 2 diabetes.

Clin Chim Acta 2010 Feb 2;411(3-4):167-71. Epub 2009 Nov 2.

Laboratory of Pharmacology and Clinical Pharmacology, Medical School, Democritus University of Thrace, Dragana Campus, 68100 Alexandroupolis, Greece.

Background: The serotonergic system contributes substantially to the regulation of glucose homeostasis and feeding. 5-HTTLPR is a serotonin transporter (5-HTT) gene-linked polymorphic region that regulates the transcriptional activity of 5-HTT. Our aim was to investigate the possible association of 5-HTTLPR polymorphism with type 2 diabetes mellitus and obesity.

Methods: Study population consisted of 252 subjects diagnosed with Type 2 DM and 211 non-diabetic subjects, all Caucasians of Greek ethnic origin. Genomic DNA was extracted from peripheral blood and analyzed for 5-HTTLPR polymorphism with a novel PCR protocol.

Results: The frequency of SS and SL genotypes of HTTLPR was significantly higher in the diabetic group (77.0%) than in the non-diabetic group (61.6%) (P<0.001). The genetic risk of Type 2 DM for subjects carrying at least one S allele was increased compared to non-diabetic subjects (OR=2.08, 95% CI=1.39-3.12). When subjects were divided according to BMI status, the frequency of S allele carriers was similar in obese and non-obese subjects.

Conclusions: The S allele of 5-HTTLPR is strongly associated with the presence of Type 2 DM. This association appears to be direct and not dependent on obesity status. Therefore, 5-HTTLPR LL genotype might be protective for development of Type 2 DM.
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http://dx.doi.org/10.1016/j.cca.2009.10.022DOI Listing
February 2010

Presence of CYP2C9*3 allele increases risk for hypoglycemia in Type 2 diabetic patients treated with sulfonylureas.

Pharmacogenomics 2009 Nov;10(11):1781-7

Laboratory of Pharmacology, Medical School, Democritus University of Thrace, Dragana Campus, 68100 Alexandroupolis, Greece.

Aims: Hypoglycemia is a common adverse effect of sulfonylurea oral hypoglycemic agents. Impaired metabolism of sulfonylureas due to gene polymorphisms in the metabolic enzyme CYP2C9 might lead to hypoglycemia. In the present study we explored the association of the CYP2C9 variant alleles CYP2C9*2 and CYP2C9*3 with the incidence of hypoglycemic events in diabetic patients receiving the sulfonylureas glimepiride and gliclazide.

Materials & Methods: A total of 92 Type 2 diabetes mellitus (T2DM) patients receiving sulfonylurea and reporting drug-associated hypoglycemia, and 84 T2DM patients receiving sulfonylurea and having never experienced hypoglycemia were included in the study. A sample of 283 nondiabetic controls that had been genotyped earlier served as a second control group. CYP2C9*2 and *3 alleles were detected by use of PCR-RFLP analysis.

Results: Frequencies of CYP2C9*1/*3 genotype and CYP2C9*3 allele were significantly lower in T2DM patients than nondiabetic controls (p = 0.003 and p = 0.017, respectively). A total of 11 out of 92 subjects (12%) experiencing hypoglycemia carried the CYP2C9*3 allele, as opposed to only 1 out of 84 subjects (1.2%) free of sulfonylurea-induced hypoglycemia. In a model adjusted for age, BMI, mean daily dose of sulfonylurea, duration of T2DM and renal function, CYP2C9*1/*3 genotype increased the hypoglycemia risk in response to sulfonylurea (odds ratio: 1.687; p = 0.011). However, no differences in CYP2C9*2 allele frequency between the two groups were found.

Discussion & Conclusion: The presence of CYP2C9*3 appears to be protective for development of T2DM. Furthermore, in T2DM patients, CYP2C9*3 increases the risk of hypoglycemia when they are treated with sulfonylureas, possibly due to impaired metabolism of these drugs. CYP2C9 genotyping might thus be a useful tool for predicting adverse effects caused by sulfonylureas and help clinicians in safer prescribing of oral hypoglycemic agents. The potential T2DM protective effect of CYP2C9*3 allele requires further investigation.
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http://dx.doi.org/10.2217/pgs.09.96DOI Listing
November 2009

Efficacy and safety of fully covered self-expandable metallic stents in biliary complications after liver transplantation: a preliminary study.

Liver Transpl 2009 Nov;15(11):1493-8

Mediterranean Institute for Transplantation and Advanced Specialized Therapies/University of Pittsburgh Medical Center, Palermo, Italy.

After liver transplantation, the most common biliary complication is the anastomotic stricture, which is followed by biliary leakage. Studies have focused on the endoscopic treatment of biliary complications in transplanted patients with duct-to-duct reconstruction, showing a success rate of 70% to 80% after orthotopic liver transplantation and of 60% after living-related liver transplantation. Once the endoscopic approach fails, surgical treatment with a Roux-en-Y choledochojejunostomy is the sole alternative treatment. The aim of this prospective observational study was to analyze the efficacy and safety of fully covered self-expandable metallic stents for the treatment of posttransplant biliary stenosis and leaks in patients in whom conventional endoscopic retrograde cholangiopancreatography (ERCP) failed. From January 2008 to January 2009, 16 patients met the criteria of endoscopic treatment failure, and instead of surgery, a fully covered stent was placed. All patients had at least 6 months of follow-up (mean follow-up of 10 months). After removal, 14 patients showed immediate resolution of both the biliary stenosis and leak. After a mean of 10 months of follow-up, only 1 patient showed biliary stenosis recurrence. No major complications occurred in any of the patients, except for stent migration in 6 patients, although these presented with no clinical consequences. In conclusion, in patients not responding to standard endoscopic treatment, the placement of fully covered metal stents is a valid alternative to surgery. A cost analysis should be performed in order to evaluate whether to treat transplanted patients suffering from biliary complications with covered self-expandable metallic stent placement as first-line therapy.
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http://dx.doi.org/10.1002/lt.21886DOI Listing
November 2009

Arterial chemoembolization/embolization and early complications after hepatocellular carcinoma treatment: a safe standardized protocol in selected patients with Child class A and B cirrhosis.

J Vasc Interv Radiol 2009 Jul 4;20(7):896-902. Epub 2009 Jun 4.

Department of Gastroenterology and Hepatology, Istituto Mediterraneo Trapianti e Terapie ad Alta Specializzazione, University of Pittsburgh Medical Center, Via Tricomi 1, 90127 Palermo, Italy.

Purpose: To assess the safety of transarterial treatments of hepatocellular carcinoma (HCC), and the statistical correlation of various patient factors with the frequency of complications, in selected patients with cirrhosis when adhering to well-standardized protocols.

Materials And Methods: Three hundred twenty consecutive patients with unresectable HCC were treated with transarterial chemoembolization, oil chemoembolization, and embolization. A total of 712 treatments were performed, with an average of 2.3 treatments for each patient. The epirubicin dose was adjusted according to defined laboratory criteria. An early complication was defined as one that occurred within 4 weeks of treatment. Complications were classified as minor and major and assessed by using clinical and laboratory data.

Results: Of the 712 procedures, 21 complications (2.9%) occurred in 17 of the 320 patients (5.3%). Major complications included acute liver failure (n = 1, 0.1%), variceal bleeding (n = 2, 0.3%), moderate-to-severe ascites (n = 4, 0.6%), sepsis (n = 3, 0.4%), cholecystitis (n = 1, 0.1%), and diverticulitis (n = 1, 0.1%). Minor complications were hepatic artery damage, including spontaneously resolved dissection (n = 3, 0.4%), mild encephalopathy (n = 1, 0.1%), and aspartate aminotransferase/alanine aminotransferase levels greater than 500 U/L (n = 5, 0.7%). The 30-day mortality rate was 0.003% (n = 1). Constitutional syndrome (P = .0001), Child-Pugh score (P = .0001), ascites (P = .037), and the Model for End-Stage Liver Disease score (P = .02) were found to have a statistically significant correlation with complications after univariate analysis. Child-Pugh score (P = .012) and constitutional syndrome (P = .003) were found to have a statistically significant correlation with complications after logistic regression analysis.

Conclusions: Transarterial treatments can be considered safe in patients with Child class A and B cirrhosis when an adjusted dose of epirubicin is used according to body surface, severity of liver disease, and white blood cell count. Accurate patient selection and procedure-related factors may reduce the frequency of complications and help preserve liver function.
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http://dx.doi.org/10.1016/j.jvir.2009.03.032DOI Listing
July 2009

Endoscopic treatment of biliary complications after liver transplantation.

World J Gastroenterol 2008 Jul;14(26):4185-9

ISMETT/UPMC, via tricomi 1, Palermo 90100, Italy.

Aim: To evaluate the efficacy of endoscopic treatment in patients who undergo OLTx or LRLTx and develop biliary complications.

Methods: This is a prospective, observational study of patients who developed biliary complications, after OLTx and LRLTx, with duct-to-duct anastomosis performed between June 2003 and June 2007. Endoscopic Retrograde Cholangiopancreatography (ERCP) was considered unsuccessful when there was evidence of continuous bile leakage despite endoscopic stent placement, or persistence of stenosis after 1 year, despite multiple dilatation and stent placement. When the ERCP failed, a percutaneous trans-hepatic approach (PTC) or surgery was adopted.

Results: From June 2003 to June 2007, 261 adult patients were transplanted in our institute, 68 from living donors and 193 from cadaveric donors. In the OLTx group the rate of complications was 37.3%, while in the LRLTx group was 64.7%. The rate of ERCP failure was 19.4% in the OLTx group and 38.6% in LRLTx group. In OLTx group, 1 patient was re-transplanted and 8 patients died. In the LRLTx group, 2 patients underwent OLTx and 8 patients died. The follow-up was 23.3 +/- 13.13 mo and 21.02 +/- 14.10 mo, respectively.

Conclusion: Although ERCP is quite an effective mode of managing post-transplant bile duct complications, a significant number of patients need other types of approach. Further prospective studies are necessary in order to establish whether other endoscopic protocols or new devices, could improve the current results.
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http://dx.doi.org/10.3748/wjg.14.4185DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2725380PMC
July 2008

Predictive factors of tumor response to trans-catheter treatment in cirrhotic patients with hepatocellular carcinoma: a multivariate analysis of pre-treatment findings.

World J Gastroenterol 2007 Dec;13(45):6022-6

Department of Radiology, Mediterranean Institute for Transplantation and Advanced Specialized Therapies (IsMeTT), University of Pittsburgh Medical Center, IsMeTT, Via Tricomi 1, Palermo 90127, Italy. [email protected]

Aim: To elucidate the pre-treatment clinical and imaging findings affecting the tumor response to the transcatheter treatment of unresectable hepatocellular carcinoma (HCC).

Methods: Two hundred cirrhotic patients with HCC received a total of 425 transcatheter treatments. The tumor response was evaluated by helical CT and a massive necrosis (MN) was defined as a necrosis > 90%. Twenty-five clinical and imaging variables were analyzed: uninodular/multinodular HCC, unilobar/bilobar, tumor capsula, hypervascular lesion, portal vein thrombosis, portal hypertension, ascites, platelets count, aspartate transaminases/alanine transaminases (AST/ALT), alfa-fetoprotein (AFP) > 100, AFP > 400, serum creatinine, virus hepatitis C (VHC) cirrhosis, performance status, age, Okuda stage, Child-Pugg stage, sex, CLIP (Cancer of the Liver Italian Program) score, serum bilirubin, constitutional syndrome, serum albumine, prothrombin activity, BCLC (Barcelona Clinic Liver Cancer) stage. Prognostic factors of response were subjected to univariate analysis and thereafter, when significant, to the multivariate analyses.

Results: On imaging analysis, complete response was obtained in 60 (30%) patients, necrosis > 90% in 38 (19%) patients, necrosis > 50% in 44 (22%) patients, and necrosis < 50% in 58 (29%) patients. Ninety-eight (49%) of the 200 patients were considered to have a MN. In univariate analysis, significant variables (P < 0.01) were: uninodular tumor, unilobar, tumor size 2-6 cm, CLIP score < 2, absence of constitutional syndrome, and BCLC stage < 2. In a multivariate analysis, the variables reaching statistical significance were: presence of tumor capsule (P < 0.0001), tumor size 2-6 cm (P < 0.03), CLIP score < 2 (P < 0.006), and absence of constitutional syndrome (P < 0.03). Kaplan-Mayer cumulative survival at 12 mo was 80% at 24 mo was 56%. MN was associated with a longer survival (P < 0.0001).

Conclusion: MN after transcatheter treatment is more common in the presence of tumor capsule, maximum diameter of the main lesion between 2 and 6 cm, CLIP score < 2 and absence of constitutional syndrome. The ability to predict which patients will respond to transcatheter treatment may be useful in the clinical decision-making process, and in stratifying the randomization of patients in clinical trials.
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http://dx.doi.org/10.3748/wjg.v13.45.6022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4250884PMC
December 2007

Efficacy of transcatheter embolization/chemoembolization (TAE/TACE) for the treatment of single hepatocellular carcinoma.

World J Gastroenterol 2007 Jun;13(21):2952-5

Istituto Mediterraneo Trapianti e Terapie ad Alta Specializzazione, University of Pittsburgh Medical Center, Italy.

Aim: To investigate the efficacy of transcatheter embolization/chemoembolization (TAE/TACE) in cirrhotic patients with single hepatocellular carcinoma (HCC) not suitable for surgical resection and percutaneous ablation therapy.

Methods: A cohort of 176 consecutive cirrhotic patients with single HCC undergoing TAE/TACE was reviewed; 162 patients had at least one image examination (helical CT scan or triphasic contrast-enhanced MRI) after treatment and were included into the study. TAE was performed with Lipiodol followed by Gelfoam embolization; TACE was performed with Farmorubicin prepared in sterile drip at a dose of 50 mg/m(2), infused over 30 min using a peristaltic pump, and followed by Lipiodol and Gelfoam embolization.

Results: Patients characteristics were: mean age, 62 years; male/female 117/45; Child-Pugh score 6.2 +/- 1.1; MELD 8.7 +/- 2.3; mean HCC size, 3.6 (range 1.0-12.0) cm. HCC size class was 6.0 cm, n = 14. Patients received a total of 368 TAE/TACE (mean 2.4 +/- 1.7). Complete tumor necrosis was obtained in 94 patients (58%), massive (90%-99%) necrosis in 16 patients (10%), partial (50%-89%) necrosis in 18 patients (11%) and poor (< 50%) necrosis in the remaining 34 patients (21%). The rate of complete necrosis according to the HCC size class was: 69%, 69%, 52%, 68%, 50% and, 13% for lesions of 6.0 cm, respectively. Kaplan-Mayer survival at 24-mo was 88%, 68%, 59%, 59%, 45%, and 53% for lesions of 6.0 cm, respectively.

Conclusion: Our study showed that in cirrhotic patients with single HCC smaller than 6.0 cm, TAE/TACE produces complete local control of tumor in a significant proportion of patients. TAE/TACE is an effective therapeutic option in patients with single HCC not suitable for surgical resection or percutaneous ablation therapies. Further studies should investigate if the new available embolization agents or drug eluting beads may improve the effect on tumor necrosis.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4171147PMC
http://dx.doi.org/10.3748/wjg.v13.i21.2952DOI Listing
June 2007
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